NEW TECHNIQUES IN MR NEUROIMAGING 1064-9689/98 $8.00 + .

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CLINICAL APPLICATIONS
OF NEUROIMAGING
IN PSYCHIATRY
Miranda H. Chakos, MD, Sharon Esposito, MD,
Cecil Charles, PhD, and Jeffrey A. Lieberman, MD

Neuropsychiatry attempts to integrate in psychiatry include: history of head trauma,

knowledge from related specialties of general
psychiatry, biologic psychiatry, child psychia-
try (particularly related to developmental dis-
orders), behavioral neurology, and geriatric
psychiatry. New techniques are dramatically
expanding current clinical applications of neu-
roimaging in neuropsychiatry. Neuroimaging
research that examines brain structure and
function relationships in neuropsychiatric dis-
orders is also enhancing our understanding of
the pathophysiology of neuropsychiatric ill-
nesses such as dementia, focal CNS insult,
schizophrenia, affective disorders, and neuro-
developmental disorders.
INDICATIONS FOR NEUROIMAGING
IN PSYCHIATRY
The earliest clinical use of neuroimaging in
psychiatry was in the diagnostic work-up of
patients presenting with neuropsychiatric
symptoms associated with medical conditions
such as multiple sclerosis and multi-infarct de-
mentia. Current indications for neuroimaging
Research for this article was supported by NIMH grant
MH 33127 at the University of North Carolina at Chapel
Hill and a NARSAD award granted to Dr. Chakos.
focal neurologic findings on physical examina-
tion, new-onset psychiatric symptoms after 40
years of age (including psychosis, affective dis-
order, and personality change), rapid onset of
psychiatric symptoms, history of neurologic
symptoms (including seizures), evidence of
cognitive impairment, abnormal electroen-
cephalogram, and abnormal lumbar punc-
ture."
CT may be part of the initial psychiatric eval-
uation when the clinician suspects such abnor-
malities as mass lesions, calcification, atrophy,
or infarction. MR imaging is recommended in
preference to CT for the evaluation of white
matter or demyelinating disorders, seizure dis-
orders, dementia, infarction, neoplasm, vascu-
lar disease, degenerative diseases such as Hun-
tington's disease, suspected localized lesions,
and in children."
Neurobehavioral dysfunction syndromes
associated with organic causes are found in a
spectrum of disorders: (1) degenerative disor-
ders such as Parkinson's disease, Alzheimer's
disease, Huntington's disease, multiple sclero-
sis, or lupus; (2) epilepsy; (3) focal insults such
as stroke or closed head injury; and (4) devel-
opmental anomalies. These neuropsychiatric
disturbances are commonly associated with

From the Department of Psychiatry (MHC) (SE) (JAL), Neuroscience's Hospital, The University of North Carolina School
of Medicine Chapel Hill; and the Department of Radiology and the Center for Advanced MR Development (CC),
Duke University Medical Center, Durham, North Carolina

MRI CLINICS OF NORTH AMERICA

VOLUME 6· NUMBER 1 • FEBRUARY 1998 155

156 CHAKOS et al
organic illness and MR imaging is an essential
part of the neuropsychiatric work-up. All of
these syndromes are associated with dysregu-
lation of brain systems including mood (limbic
system), arousal (brainstem), perception (corti-
cal association areas), executive functions
(frontal lobes), or behavioral inhibition and
control (orbital frontal lobes). Although each
clinical disorder has specific pathophysiologic
characteristics, they can cause similar neuro-
psychiatric disturbances that often reflect the
location and extent of the associated brain le-
sion. 39, 53
DEMENTIA
Cortical Dementia
Dementias can be classified into cortical and
subcortical subtypes. Alzheimer's disease
(AD) and Pick's disease are the major cortical
dementias. AD accounts for 54.5% of dementia
in persons older than 65 years of age. Patients
with AD generally have larger ventricles and
more severe medial and temporal lobe atrophy
than do patients with nonspecific dementias.v
Patients with Pick's disease have striking fron-
totemporal or focal anterior cortical atrophy.
MR spectroscopy, particularly utilizing
phosphorus elp), has been useful clinically in
studying the pathophysiology of neurodegen-
eration in AD. Phosphorus MR spectroscopy
allows for direct measurement of brain mem-
brane phospholipids and high energy phos-
phate metabolism. Phosphomonoester (PME)
is a precursor of membrane phospholipids,
whereas phosphodiester (PDE) results from
breakdown products of the membrane. With
increasing age, there is a significant decrease in
PME and a significant increase in PDE, which
corresponds to a decreased synthesis and in-
creased breakdown of membrane phospholip-
ids, respectively." AD studies employing 31p
MR spectroscopy have shown an increase in
brain PME early in the course of the disease,
followed by increase in PDE later."
Subcortical Dementia
Subcortical dementias, such as those seen
in Huntington's disease, Parkinson's disease,
multiple sclerosis (MS), and AIDS dementia
complex (ADC) are often characterized by
damage to the basal ganglia, thalamus, and
deeper brainstem and are accompanied by
movement disorders. In Parkinson's disease
narrowing of the pars compacta of the substan-
tia nigra in the midbrain may be detected by
MR imaging. For patients who have medically
intractable symptoms of Parkinson's disease,
MR-guided stereotactic targeting and micro-
electrode recording techniques are used in ste-
reotactic pallidotomy procedures to destroy a
portion of the globus pallidus and thereby de-
crease muscle rigidity." In Huntington's dis-
ease, striatal atrophy may be measured by lin-
ear (bicaudate index), transverse diameter of
the head of the caudate nucleus, or by area
measurements on CT and MR images." In MS,
plaques are seen on MR images and the
amount of plaques is significantly correlated
to the degree of cognitive impairment.e" Clin-
ical neuroimaging findings in AIDS using CT
typically demonstrate cortical atrophy, ven-
tricular enlargement, and sulcal enlargement
that increase in severity with progression of
HIV infection.o " but CT is relatively insensi-
tive to the presence of ADC. Morphometric
analysis of MR imaging in patients with ADC
compared with AIDS patients without demen-
tia have shown that patients with ADC have
greater gray-matter volume reduction in the
basal ganglia and posterior cortex.l-? Positron
emission tomography (PET) studies of glucose
metabolism enhance the ability to distinguish
nondemented AIDS patients, who have corti-
cal hypermetabolism, from ADC patients, who
have hypometabolism in cortical and subcorti-
cal gray matter. 54, 83
Proton (lH) MR spectroscopy, which mea-
sures the metabolites N-acetyl aspartame
(NAA), creatinine, and choline, has enhanced
our understanding of the pathophysiology of
neurodegeneration in subcortical dementia.
NAA is a marker for neuronal damage or de-
struction.Y" Reduced in vivo levels of NAA
have been reported in MS.69 The reduction in
NAA may be reversible and the reversibility
depends on the extent of neuronal damage."
Reduced NAA levels are also seen in HIV de-
mentia. 18, 68 Decreased NAA in Huntington's
disease has been found to be associated with
increases in glutamine and glutamate levels,
which are consistent with the excitotoxic
hypothesis of this disease." Patients with
Creutzfeldt-Iakob (C-J) disease demonstrate a
40% reduction in NAA levels, a 10% reduction
in creatinine levels, and 30% reduction in inosi-
tollevels when compared with controls."
 CLINICAL APPLICATIONS OF NEUROIMAGING IN PSYCHIATRY
Vascular Dementia
Vascular dementia is a combined subcorti-
cal-cortical dementia that accounts for 29% of
all dementia. No brain MR or CT findings are
pathognomonic for vascular dementia.P The
lacunar type of vascular dementia, which is
often accompanied by silent strokes and a
progressive course, is easily confused with
Alzheimer's-type dementia (DAT). The mea-
surements of cerebral blood flow and metabo-
lism displayed using PET distinguish vascular
dementia from DAT. Vascular dementia has a
multifocal pattern of reduced perfusion,
mostly in subcortical regions including the
basal ganglia, thalamus, and cerebellum,
whereas in DAT there is a diffuse decrease in
cerebral perfusion in the temporoparietal and
frontal association cortex. In both vascular de-
mentia and DAT the severity of cognitive im-
pairment correlates directly with the volume
of impaired cerebral glucose metabolism as
seen on PET studies/"
EPILEPSY
Clinically, a major goal in evaluating intrac-
table epilepsy is the task of isolating the epilep-
togenic locus. Accurate localization provides
information that is helpful both for proper di-
agnosis of epilepsy type and for choice of phar-
macologic or surgical treatment. Such localiza-
tion has entailed using a variety of modalities,
including long-term electroencephalogram
(EEG) monitoring with telemetry and invasive
EEG monitoring with depth electrodes. Recent
advances in structural and functional neuro-
imaging have made invasive EEG recording
less necessary. High-resolution CT of patients
with focal epilepsy reveals a lesion in 60% to
70% of cases. MR imaging is used routinely
and is superior to CT scans in detecting most
epilepsy-related lesions, including tumors,
vascular malformations, and medial temporal
sclerosis. The diagnosis of hippocampal pa-
thology can be improved by quantitative MR
volumetric studies." Proton MR spectroscopy
has also been used to detect decreases in NAA
in the mesial temporal lobe of patients with
hippocampal sclerosis."
Once a lesion is detected in a seizure patient
who has structural imaging studies, functional
studies are required to determine if a structural
lesion is responsible for the seizure and might
eventually be excised. Efforts to identify the
locus of epileptic activity have evaluated focal
157
changes in blood flow and metabolism that
may either accompany or underlie epileptic
activity using single photon emission com-
puted tomography (SPECT) or PET. SPECT
utilizing Technetium-99 hexamethylpropyl-
ene amine-oxime (99Tc-HMPAO) as the tracer
will demonstrate hypoperfusion in an area ex-
tending beyond the epileptogenic region dur-
ing the interictal period. The sensitivity of in-
terictal focus detection ranges from 40% to
80%.83 Postictal and ictal SPECT typically show
hyperperfusion ipsilateral to the epileptogenic
focus.F PET is generally utilized interictally
to demonstrate the locus of epileptic activity,
either by detecting areas of altered blood flow
using oxygen 15 or altered metabolism using
18F-fluorodeoxyglucose. PET has superior spa-
tial and contrast resolution compared with
SPECT, but it is more expensive and ictal stud-
ies are difficult owing to the short half-life of
positron-emitting radioisotopes. Localized in-
terictal hypoperfusion and hypometabolism in
the epileptogenic area as shown by PET are
reliable confirmatory findings in the presurgi-
cal assessment of temporal lobe epilepsy pa-
tients."
Functional MR imaging holds the promise
of being a less expensive and less invasive im-
aging technique for identifying the locus of
epileptic activity. A particular benefit of func-
tional MR imaging in the management of epi-
lepsy is the ability to quickly combine high-
resolution anatomic studies with functional
studies, without the need for coregistration of
different imaging modalities. Combining EEG
with functional MR imaging during imaging
will allow for the acquisition of temporally
correlated neurophysiologic and imaging in-
formation that will increase the flexibility in
identifying the locus of epileptic activity."
FOCAL CNS INSULTS
Cerebral Vascular Accident
Cerebral neuroimaging is the only sure
means by which to differentiate between cere-
bral ischemia and hemorrhage and in some
patients is the only way to differentiate stroke
from tumors or other mass lesions. In clinically
suspected stroke, imaging must be done imme-
diately to formulate and initiate treatment in
a timely fashion. CT is an effective means of
differentiating hemorrhage from infarct early
after clinical onset of stroke. MR imaging, how-
ever, allows precise anatomic localization of
cerebral infarction. In addition, MR angiogra-
158 CHAKOS et al
phy provides a noninvasive view of the major
cerebral arteries.
Conventional MR imaging demonstrates
ischemic abnormalities by detecting changes in
brain tissue relaxation times, but such changes
generally occur only after several hours, at
which point there is limited opportunity for
therapeutic intervention with thrombolytic
and putative neuroprotective agents." There
is great interest in the future use of diffusion
and perfusion MR imaging to visualize isch-
emic changes at the earliest possible moment
and to monitor progress of thrombolytic and
neuroprotective therapies.P
Traumatic Head Injury
Traumatic head injury accounts for signifi-
cant neuropsychiatric disability, with motor
vehicle accidents being the most common
cause. Head injuries may be categorized as
either open with acute presentation or closed
with subtle or chronic presentation in which
the bony cranium remains intact. These injur-
ies, particularly intermediate and minor types,
may present only with behavioral, memory, or
affective changes rather than severe neurologic
deficit. The mechanisms of traumatic brain in-
juries include mechanical injury, diffuse axo-
nal injury, hypoxia, and free radical formation.
The secondary effects of such traumas, how-
ever, cause the neuropsychiatric sequelae and
complicate rehabilitation. These effects include
hypoxemia, hypotension, hypercapnia, ane-
mia, hyponatremia, hypoglycemia, infection,
and seizures. There is evidence that both neu-
roanatomic and neurochemical changes alter
mood and affect." The neurochemical changes
noted include alterations in the norepineph-
rine, serotonin, dopamine, and acetylcholine
systems. Secondary neurotoxicity caused by
free-radical formation may affect neuronal
tracts, particularly of the hypothalamus, basal
ganglia, limbic system, and frontal cortex,
leading to affective and behavioral changes.
Neuropsychiatric sequelae secondary to trau-
matic brain injury often present with personal-
ity changes, intellectual and affective changes,
psychotic features, delirium, and seizure dis-
orders. Two important factors that determine
the severity of neuropsychiatric sequelae sug-
gest the relevancy of neuroimaging in this clin-
ical setting: (1) extent and severity of brain
lesion; and (2) anatomic location of Iesion.f
Lesions in the dorsolateral frontal cortex are
associated with slowness, apathy, blunted af-
fect, social withdrawal, and abulia. Lesions in
the orbital surface of the frontal lobes and ante-
rior temporal lobes are associated with rage
and violence as well as aggressive sexual be-
havior. Intellectual and cognitive dysfunctions
include changes in attention, concentration,
and memory leading to impairment in infor-
mation processing and abstract thinking. MR
imaging and MR spectroscopy provide infor-
mation related to the specific lesions and are
clinically significant to the neuropsychiatrist
and to rehabilitative efforts. Neuroimaging as-
sists in diagnosis and rehabilitation of specific
skills and in psychopharmacotherapy for the
areas of injury.
PSYCHIATRIC DISORDERS
Schizophrenia
At the present time there are no structural
findings that can be considered diagnostic for
schizophrenia. Thus, the only clinical indica-
tion for the use of imaging is to rule out other
brain pathology underlying the psychotic be-
havior. Neuroimaging studies have made im-
portant contributions to the understanding of
the neurobiology of schizophrenia, however.
The most replicated findings in brain dysmor-
phology in schizophrenia include ventricular
enlargement-s 27, 51,103 and sulcal dilatation.f 66, 90
In addition, widespread cortical volume def-
icits selective to gray matter have been re-
ported.F: 106, 107 These findings establish the
presence of generalized global brain dysmor-
phology in schizophrenia. One of the more
robust constellations of findings in the neuro-
imaging of schizophrenia concerns the absence
or loss of normal structural brain symmetries,
with reports of lateralized abnormalities in the
temporal lobe substructures such as the amyg-
dala, hippocampus, and superior temporal gy-
rus, in the basal ganglia, and in numerous cor-
tical subregions' 6, 29 MR imaging of either
the temporal lobes as a whole, or of more spe-
cific regions, such as the superior temporal
gyrus or left parahippocampal gyrus, has re-
ported volume reductions in schizophrenic pa-
tients." 12, 91, 97, 107 The limbic structures in the
mesial temporal lobe have also been reported
to have abnormalities. Several MR studies de-
scribe amygdala-hippocampal complex vol-
ume reduction in schizophrenic patients?' 9, 11, 98
Some studies have failed to detect volume dif-
 CLINICAL APPLICATIONS OF NEUROIMAGING IN PSYCHIATRY
ferences in the hippocampus, however." 99, 107
Similar conflicting findings have been reported
in regard to basal ganglia volumes, with some
studies reporting reduced volume" and others
reporting increased volume.? 49 A prospective
study of first-episode schizophrenics suggests
that caudate nuclei enlargement in schizo-
phrenic patients is an effect of chronic neuro-
leptic treatment."
Functional MR imaging studies have gener-
ally reported decreased metabolism and blood
flow in the basal ganglia of never-medicated
schizophrenic subjects." Low metabolic rates
in the striatum may predict positive clinical
response to neuroleptics," and neuroleptic
treatment appears to increase basal ganglia
metabolism." Another well-replicated finding
is that of decreased activation of the dorsolat-
eral prefrontal cortex in schizophrenic patients
when they are challenged with the Wisconsin
Card Sorting Test, a task that requires patients
to use working memory to make decisions
based on past experiences and to change their
behavior based on error information.!"
The findings from receptor imaging studies
of the dopamine D2 system in schizophrenia
have thus far been inconclusive. A N-
[llC]methyl-spiperone PET study has demon-
strated a two-to threefold increase in D2 re-
ceptor density in the caudate nuclei of
schizophrenic patients.!" Mean striatal D2 re-
ceptor densities, however, were not found to
differ between neuroleptic-naive schizo-
phrenic subjects and controls in two studies
using [llC]raclopride as the radioligand
tracer. 32,43 Differing pharmacokinetics of the
two ligands used in these PET studies and
their differing affinities for dopamine receptor
subtypes may account for the differences in
these findings.
Affective Disorders
Small caudate volumes have been demon-
strated in mixed-age samples of depressive pa-
tients and have been interpreted as evidence
of a disruption to the caudate-prefrontal path-
way." Patients with late-life depression have
been found to have an increase in the severity
of high-intensity signals in the periventricular
white matter and in subcortical regions com-
pared with nondepressed controls.i" 89, 105
Several groups have found an association be-
tween areas of increased signal intensity and
cerebrovascular risk factors as outlined by
159
the American Heart Association, including
hypertension, diabetes, smoking, and atrial
fibrillation.55, 57
Most studies report global or focal decrease
in glucose metabolism and blood flow in
patients with major depressive disorder
(MDD).4, 5, 73, 100 Focal decreases in metabolism
are particularly prominent in the frontal lobes,
left anterior cingulate gyrus, left dorsolateral
prefrontal cortex, and basal ganglia." 5, 73 Some
investigators, however, have found that hypo-
metabolism is present only during resting
state, but does not persist during a cognitive
challenge." Others report no decrease in rest-
ing cerebral perfusion in mixed age samples
of MDD patients. 65,80 Some investigators report
a normalization of metabolism and flow with
successful treatment with antidepressant or
electroconvulsive therapy.58,72 Other investiga-
tors report no change in resting regional cere-
bral blood flow with successful treatment of
depression."
Although qualitative and quantitative MR
imaging has enhanced our understanding of
the pathophysiology of MDD, the diagnostic
value of these techniques remains minimal.
Reasons for conflicting findings are that scan-
ning techniques, imaging protocols, methods
of data acquisition, and image analysis vary
considerably across groups, the clinical groups
examined vary across studies, and most stud-
ies use highly selective clinical groups present-
ing at university settings, which limits the gen-
eralizability of the findings.
DEVELOPMENTAL DISORDERS
Neuropsychiatric developmental disorders
are believed to result from deviation from nor-
mal brain development. The most frequently
studied developmental disorders include au-
tism, attention deficit hyperactivity disorder,
dyslexia, Down's syndrome, Tourette's syn-
drome, and childhood-onset schizophrenia.
The clinical utility of neuroimaging in these
neuropsychiatric disorders currently is to rule
out other causes for the symptoms. Neverthe-
less, MR imaging provides a new avenue of
investigation into the pathogenesis and patho-
physiology of these illnesses.
Autism
MR imaging studies of autistic subjects re-
port enlarged ventricles and reduced cerebel-
160 CHAKOS et al
lar and superior-posterior vermis size.":" Cor-
tical malformations including polymicrogyria,
schizencephaly, and macrogyria have also
been described." These abnormalities are be-
lieved to arise from disturbances in neuronal
migration that occur in the second trimester of
gestation. PET abnormalities include localized
regions of hypometabolism in the cortical asso-
ciation areas, especially in the parietal, occipi-
tal, and temporal lobes." MR spectroscopy
data seem to indicate hypermetabolism in the
dorsal prefrontal cortex, which is suggestive
of enhanced degradation of cell membranes in
this area."
Attention Deficit Disorder
Neuroimaging studies on the pathophysiol-
ogy of attention deficit disorder report reduced
volume of the corpus callosum, sulcal widen-
ing, and caudate nuclei asymmetry.v- 37, 46, 64
Functional imaging studies show decreased
metabolism in the striatal region and reduced
metabolic rates in sensorimotor, auditory, and
occipital regions in adolescents.f
Tourette's Syndrome
Structural imaging studies in Tourette's syn-
drome report reduced volume of the corpus
callosum and left lentiform nucleus as well
as absence of asymmetry in the lentiform nu-
cleF5, 94 Functional imaging studies corrobo-
rate basal ganglia pathology with the finding
of hypometabolism in the ventral striatum."
Dyslexia
Neuroimaging findings on the pathophysi-
ology of dyslexia remain preliminary. Several
MR studies report an absence or reversal of the
leftward asymmetry of the planum temporale
seen in normal subjects.v" Other studies have
failed to replicate findings of group differences
in hemispheric asymmetry/"" PET studies
have demonstrated an abnormal decrease in
activation of the posterior portions of the pla-
num and increases in activation in the medial
temporal lobe during phonologic processing
tasks,": 85 which may reflect activation of com-
pensatory pathways or inefficient metabolic
processing.
Childhood-Onset Schizophrenia
Because of rarity, the largest neuroimag-
ing study of childhood-onset schizophrenia
(COS), defined as onset of psychotic symptoms
prior to 12 years of age, is a cohort of treatment-
refractory patients being followed prospec-
tively in an ongoing study at the Child Psychi-
atry Branch of the National Institutes of Mental
Health.P 38,48 MR imaging assessment of these
patients found a lack of normal right-greater-
than-left asymmetry of the hippocampus, but
no mean differences in the volume of the tem-
porallobe, amygdala, hippocampus, or supe-
rior temporal gyrus." In addition, subjects had
smaller total cerebral volume and midsagittal
thalamic area, larger basal ganglia, and a trend
toward larger ventricles." Overall, results of
neuroimaging investigations add to the data
from clinical and neuropsychologic reports, in-
dicating a continuity between COS and adult-
onset schizophrenia.v 84
Down's Syndrome
The initial elucidation of homogeneous sub-
types of retardation syndromes such as
Down's syndrome has resulted in use of neu-
roimaging to examine the neurobiologic effects
of specific genetic defects. Despite the causal
homogeneity in patients with Down's syn-
drome, finding appropriate contrast groups
continues to be a methodologic challenge ow-
ing to the difficulty in controlling for con-
founding variables such as IQ, which are likely
to correlate with cerebral structural and func-
tional measures. Despite these difficulties, nu-
merous investigators have consistently re-
ported decreased whole-brain and gray-matter
volumes, especially in gray matter of the fron-
tal lobes and in the limbic region, hypoplasia
or atrophy of the corpus callosum, and re-
duced volume of the cerebellum and vermian
Iobules/" 88, 101 Histopathologic studies that
demonstrate smaller structures in midterm fe-
tuses and presenile cortical degeneration asso-
ciated with the accumulation of amyloid
plaques and neurofibrillary tangles suggest
that the cortical abnormalities may be second-
ary to both hypoplastic and degenerative pro-
cesses. 88,89 Preliminary PET studies report ab-
normal metabolic patterns involving frontal
and parietal regions and language systems
in particular."
 CLINICAL APPLICATIONS OF NEUROIMAGING IN PSYCHIATRY
CONCLUSIONS
Methodologic Problems
Inconsistency in report of brain pathomor-
phology in neuroimaging studies of neuropsy-
chiatric disorders, particularly in regard to
some of the more localized findings, has oc-
curred in part because neuroimaging tech-
niques are continually developing and im-
proving. Thus, depending on available re-
sources and the timing of a study, laboratories
have adopted different approaches for image
acquisition and analysis. In addition to techno-
logic differences, laboratories have used differ-
ent techniques for accounting for normal varia-
tions due to age and head size, may not have
a standardized head position, and may have
defined specific brain structures differently.
Sampling differences in subject selection and
availability, use of small sample sizes, and use
of control groups who are not matched for age,
gender, and IQ may also account for inconsis-
tent reports.
Future Directions
Despite the problems enumerated in the
prior section, neuroimaging has contributed
immeasurably to the study of brain structure
and pathogenesis in neuropsychiatric illness,
and will continue to provide investigators with
an opportunity to answer fundamental ques-
tions about the pathophysiology of neuropsy-
chiatric illnesses. The development of new MR
pulse sequences and the use of higher mag-
netic field strengths will provide an improved
resolution of even the smallest regions of inter-
est. Use of automatic segmentation algorithms
for determination of structure volumes will
enhance our ability to reduce error in repeated
measurements and will permit longitudinal
multicenter neuroimaging studies of large
samples of patients with neuropsychiatric dis-
orders, which will answer important questions
about disease progression. Use of new tech-
nologies such as shape analysis will provide
us with additional and perhaps more sensitive
measures for detecting group differences be-
tween patients and control subjects. Acquisi-
tion of structural and functional images in the
same subjects will give us important informa-
tion about the brain structure-function rela-
tionship. The use of high-resolution electroen-
cephalography in conjunction with functional
161
MR imaging will allow us to image brain elec-
trical changes with a temporal resolution of
milliseconds, and a spatial resolution compa-
rable to current MR imaging standards. Im-
provements in the ability to stratify subjects
with respect to the degree of genetic risk for
a disorder by using genetic markers and with
respect to degree of exposure to prenatal and
obstetric complications will permit investiga-
tors to use neuroimaging to determine the ef-
fects of genetic and nongenetic factors on the
neurobiologic substrate of these disorders.
With continued advances in neuroimaging
and genetic analysis technologies, neuroimag-
ing is likely to contribute to an improved diag-
nostic classification of neuropsychiatric disor-
ders into biologically homogeneous units
whose treatment responsiveness will be more
uniform. Advances in receptor imaging meth-
odologies may also influence treatment deci-
sions for individual patients with regard to
the class and dosage of specific pharmacologic
agents used. These advances will permit ear-
lier and more accurate diagnosis, which may
prevent disease progression and improve as-
sessment of the treatment response.
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