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High-resolution brain SPECT imaging in ADHD

Authors:
Daniel G. Amen at The Amen Clinics
Daniel G. Amen
Blake D. Carmichael
Blake D. Carmichael
Blake D. Carmichael
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Abstract and Figures

Children and adolescents with ADHD were evaluated with high-resolution brain SPECT imaging to determine if there were similarities between reported PET and QEEG findings. Fifty-four children and adolescents with ADHD by DSM-III-R and Conners Rating Scale criteria were evaluated. A non-ADHD control group was also studied with SPECT. Two brain SPECT studies were done on each group, a resting study and an intellectual stress study done while participants were doing a concentration task. Sixty-fiver percent of the ADHD group revealed decreased perfusion in the prefrontal cortex with intellectual stress, compared to only 5% of the control group. These are findings consistent with PET and QEEG findings. Of the ADHD group who did not show decreased perfusion, two-thirds had markedly decreased activity in the prefrontal cortices at rest.
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Annals
of
Clinical
Psychiatry,
Vol.
9, No. 2,
1997
High-Resolution
Brain SPECT Imaging
in
ADHD
Daniel
G.
Amen, M.D.
1,2
and
Blake
D.
Carmichael,
BA.
1
Children
and
adolescents
with
ADHD
were
evaluated
with
high-resolution
brain
SPECT
imaging
to
determine
if
there
were
similarities
between
reported
PET and
QEEG
findings.
Fifty-four
children
and
adolescents
with
ADHD
by
DSM-III-R
and
Conners
Rating
Scale
criteria
were
evaluated.
A
non-ADHD
control
group
was
also
studied
with
SPECT
Two
brain
SPECT
studies
were
done
on
each
group,
a
resting
study
and an
intellectual
stress
study
done
while
participants
were
doing
a
concentration
task.
Sixty-five
percent
of the
ADHD
group
revealed
decreased
perfusion
in the
prefrontal
cortex
with
intellectual
stress, compared
to
only
5% of the
control
group.
These
are
findings
consistent
with
PET and
QEEG
findings.
Of
the
ADHD
group
who did not
show
decreased
perfusion,
two-thirds
had
markedly
de-
creased
activity
in the
prefrontal
cortices
at
rest.
KEY
WORDS: Attention
deficit
hyperactivity
disorder; single-photon emission computed tomography
(SPECT); prefrontal cortex.
INTRODUCTION
Brain
SPECT
(single-photon emission computed
tomography) imaging
is a
nuclear medicine study
which
may
offer
the
most widely available
and
widely
applicable measure
of
neuronal behavior (1).
SPECT
measures cerebral blood
flow
and, indirectly, brain
metabolism (2).
In
studying psychiatric patients with
brain
SPECT
imaging,
researchers
have found
cere-
bral
perfusion patterns
for
many
different
psychiatric
conditions (3). Chiron
et al. (4)
recently reported
normative data
for
children demonstrating that
the
brain
of a 2- to
3-year-old child shows
the
same rela-
tive cerebral blood
flow
pattern
as the
adult brain.
Attention deficit hyperactivity disorder
(ADHD)
has
been studied with SPECT, PET,
and
QEEG
stud-
ies.
Lou et al.
(5,6) reported
SPECT
hypoperfusion
in
the
regions
of the
prefrontal cortex
and the
basal
ganglia which normalized
with
stimulant medication.
Expected
cortical
areas
failed
to
activate during
a
concentration task. Sieg
et al. (7)
reported
SPECT
findings
in 10
patients
with
the
DSM-III-R diagnosis
of
attention deficit hyperactivity disorder
(ADHD),
showing
uptake asymmetries
with
less
activity
in the
left
frontal
and
left
parietal regions
in
comparison
to
control patients. Zametkin
et al. (8)
published
PET
data demonstrating that adults with
ADHD
had
pre-
frontal
cortical deactivation
in
response
to an
intel-
lectual
challenge,
as
opposed
to
increased prefrontal
cortical activity that
was
seen
in
normal
"control"
adults.
The
same
group's
PET
studies
of
children
and
teenagers
with
ADHD,
however, were more equivo-
cal.
Boys
with
ADHD
showed
no PET
differences
from
controls,
while girls
in the
study
had
reduced
global
metabolic activity (9).
Lubar,
who has
performed spectral analysis
of
QEEGs
(quantified computerized EEG)
on
children
and
adolescent
patients with
ADHD,
found that
when
these patients performed
a
concentration task,
such
as
reading
or
copying figures,
there
was an in-
crease
in
frontal lobe theta activity (slow brain wave
activity)
rather
than
the
expected
decrease
in
frontal
lobe slow wave
activity
that
is
found
in
normal con-
trols
(10, 11).
The
above
findings
suggest abnormal activity
in
the
prefrontal cortex
in
ADHD.
Lubar, with
QEEG
spectral analysis,
and
Zametkin,
in the
adult
PET
study,
report that these
difficulties
become more pro-
nounced during
a
concentration
task.
The
more peo-
'The Amen Clinic
for
Behavioral Medicine,
350
Chadbourne
Road, Fairfield,
California
94585.
^To
whom
correspondence should
be
addressed
at The
Amen
Clinic
for
Behavioral Medicine,
350
Chadbourne Road,
Fairfield,
California
94585.
81
1040-1237/97/0600-0081$12.50/1 C
1997 American Academy
of
Clinical
Psychiatrists
82
Amen
and
Carmichael
ple
with
ADHD
try to
concentrate,
it
appears,
the
worse thinking
and
concentrating becomes
for
them.
In
this paper
we
report
our
results
on 54
chil-
dren
and
adolescents
who met the
DSM-III-R crite-
ria
for
ADHD
and
compare them
to 18
children
from
a
psychiatric clinical population
who did not
meet
the
criteria
for
ADHD
or
ADD, residual type.
We
hypothesized that children with
ADHD
would
experience
the
same prefrontal lobe hypoperfusion
with
intellectual challenge
on
brain
SPECT
imaging
as
reported
by
Zametkin with
PET
studies
in
adults
and
Lubar with
QEEG
spectral
analysis
in
children
and
adolescents.
METHOD
We
performed brain
SPECT
imaging
on 54
medication-free children
and
adolescents
from
a
psychiatric
outpatient
clinic
who met the
DSM-III-R
criteria
for
attention
deficit
hyperactivity disorder.
In
addition, each
of
these children
or
adolescents
had a
parent rating score
of
greater than
18 on the
short
form
of the
Conner's Parent-Teacher Rating
Scale.
We
compared this group
to 18
medication-
free
children
and
adolescents
from
a
psychiatric out-
patient clinic population
who did not
meet
the
criteria
for
attention deficit hyperactivity disorder
or
attention deficit disorder, residual type,
who had a
score
of
less than
10 on the
Conner's
Parent-
Teacher Rating
Scale,
and who
also
had a
brain
SPECT
study
as
part
of
their clinical workup.
See
Table
1 for age and sex
comparisons. Diagnoses were
made
by a
board-certified child
and
adolescent psy-
chiatrist
(DA) using information
from
clinical inter-
views with
the
children
and the
parents,
the
Conner's
Parent-Teacher
Checklist,
and
Decision-
base,
a
commercially available, structured DSM-III-
R
computerized interview
filled
out by the
parents.
The
ultimate diagnostic decision remained with
the
psychiatrist
utilizing
all of the
data.
Table
1. Age and Sex
Distribution
n
Male
(%)
Age
Mean
Range
ADHD
54
46
(85)
11
6-17
Non-ADHD
18
15
(84)
11
7-18
In
each case,
a
resting
and an
intellectual
stress brain
SPECT
study were performed. During
the
resting phase
the
child
or
adolescent
was
placed
in
a
quiet room
and
intravenous access
was
obtained
via
small-gauge butterfly.
The
patients remained
quiet
for 15 min
with their eyes open
to
allow their
mental state
to
equilibrate
to the
environment.
Ceretec (99m
Tc
hexamethylpropylene amine oxime)
was
then injected.
A
tomographic brain study
was
performed
approximately
60 min
later using
a
Picker
Prism
3000 gamma camera with
fan
beam collima-
tors.
Data were
acquired
in 128 x 128
matrices.
One
hundred twenty images with
3° of
separation span-
ning
360°
of
rotation were obtained.
The
data were
prefiltered using
a
Ramp filter with
a
high
cutoff.
Attenuation correction
was
performed using
a
linear
method. Coronal, sagittal,
and
transaxial
to-
mographs were reconstructed with
a
slice thickness
of
approximately
9 mm. The
transaxial tomographs
were parallel
to the
orbital-meatal line.
The to-
mographs were displayed using
a
standardized color
scale.
The
tomographs obtained were those
of
rela-
tive
blood
flow,
rather than absolute quantification
of
blood
flow.
Relative blood
flow
means blood
flow
in
relationship
to the
brain's
own
activity
(how active
or
inactive brain
areas
are
compared
to the
whole
brain). This
is
standard procedure
in
most
SPECT
labs.
The
tomographs were displayed using
a
stand-
ardized color
scale.
Several days later
the
patient returned
for the
intellectual
stress study. Each patient
was
prepared
in
the
same manner
for
this part
of the
study. How-
ever,
after
the iv was
started
the
patient performed
a
standardized continuous performance task (devel-
oped
by
Conners, distributed
by
MHS).
The
task
was
performed
for 5 min
before
and 10 min
after
the
iso-
tope
was
injected through
the iv. The
scan
was
then
performed
and
processed
as
described above.
The
brain
SPECT
studies were then read
by the
nuclear medicine physician,
who was
blind
to
diag-
nosis.
Listed
in
Tables
2 and 3,
relative
activity
in
each brain area
was
assessed
by
visual inspection
and
assigned
a
qualitative value
on a
scale
of 1+ to 4+
for
overactive areas
and -1 to -4 for
underactive
ar-
eas.
These
readings
are
relative
to
other areas
of the
brain using
the
cerebellum
as the
most active area
of
the
brain.
The
clinical
utility
for
this procedure
is
well
chronicled
by
many other studies
(12-14).
Com-
parisons between
ADHD
and
non-ADHD groups
were made
using
the
Fisher's
exact test. Two-sided/*
values
are
reported.
Brain
SPECT Imaging
in
ADHD
83
Tbble
2.
Comparison
of
Brain
SPECT
Studies
of the
ADHD
Group
vs. the
Non-ADHD
Clinic
Group
at
Rest
3
Prefrontal
decreased
activity
L
R
Frontal
dorsal
focal
activity
L
R
Medial
frontal
lobe
activity
Temporal
lobe
L
R
Parietal
lobe
focal
L
R
Occipital
lobe
L
R
Cerebellum
focal
L
R
Basal
ganglia
diffuse
Basal
ganglia
focal
L
R
Limbic
diffuse
Limbic
focal
L
R
Patchy
cortical
uptake
Dilated
ventricles
ADHD
(%)
(N
= 54)
18
(33)
6(11)
21
(38)
20
(37)
37
(68)
11
(20)
7(13)
12
(22)
10
(19)
0(00)
0(00)
0(00)
0(00)
5(09)
5(09)
5(09)
27
(50)
10
(19)
8(15)
11
(20)
2(04)
Non-ADHD
(%)
(N
= 18)
3(17)
4(22)
2(11)
5(27)
11
(61)
0(00)
2(11)
2(11)
2(11)
0(00)
0(00)
1(05)
1(05)
2(11)
1(05)
0(00)
9(50)
5(28)
1 (05
1
(05)
1
(05)
Two-sided
p
value
0.049
ns
0.049
ns
ns
0.063
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
2
Activity
listed
as
abnormal
was
increased
activity
unless
otherwise
noted.
RESULTS
Tables
2 and 3
present
the
data comparing
the
ADHD group
to the
non-ADHD clinic group
at
rest
and
under intellectual stress.
Of
significance,
65% of
the
children
and
adolescents diagnosed with ADHD
had
significant
prefrontal cortex
hypoperfusion
in re-
sponse
to an
intellectual challenge (Fig.
1),
com-
pared
to
only
5% of
those
clinical
patients
who did
not
have
ADHD
or ADD (p <
0.0001).
Of the 19
ADHD patients (34%)
who did not
suppress their
prefrontal
lobe activity
with
intellectual stress,
12
(63%)
had
decreased
prefrontal
lobe
activity
at
rest,
predominantly
on the
left
side. Focal areas
of in-
creased activity
in the
frontal
lobes, especially
on the
left,
were also noted
in the
ADHD population
at
rest
and
during intellectual stress. This
is
consistent
with
data presented
by
Jaeger (15).
In
addition,
a
higher
percentage
of
increased
activity
was
also noted
in the
temporal
lobes,
again
most notably
on the
left.
DISCUSSION
Prefrontal
lobe
functions
include attention span,
concentration, judgment, activity level, critical think-
ing,
and
impulse
control
(16).
It is not
surprising,
therefore,
to see
that
in a
significant
majority
of the
ADHD cases (87%), there
was
prefrontal lobe
hy-
poperfusion
with
intellectual stress (65%)
or de-
creased
activity
in the
prefrontal cortex
at
rest
(22%).
With
hypoperfusion
in the
prefrontal cortex there
may
be a
loss
of
inhibition normally exerted
by the
frontal
cortex, resulting
in
hyperactive, impulsive,
and
inattentive behaviors.
Temporal
lobe
dysfunction
in a
percentage
of
chil-
dren
and
adolescents
with
ADHD
was a
surprise
to
84
Amen
and
Carmichael
"Table
3.
Comparison
of
Brain
SPECT
Studies
of the
ADHD
Group
vs. the
Non-ADHD
Clinic
Group
During
a
Concentration
Task
0
Prefrontal
intellectual
stress
Increase
No
change
Decrease
Frontal
dorsal
focal
activity
L
R
Medial
frontal
lobe
activity
Temporal
lobe
L
R
Parietal
lobe
focal
L
R
Occipital
lobe
L
R
Cerebellum
focal
L
R
Basal
ganglia
diffuse
Basal
ganglia
focal
L
R
Limbic
diffuse
Limbic
focal
L
R
Patchy
cortical uptake
Dilated
ventricles
ADHD
(%)
(N
= 54)
15
(27)
4(07)
35
(65)
19
(35)
16
(30)
7(12)
11
(20)
7(13)
10
(19)
8(16)
0(00)
0(00)
0(00)
0(00)
7(13)
5(09)
5(09)
20
(38)
7(13)
6(11)
7(13)
0(00)
Non-ADHD
(%)
(N
= 18)
15
(83)
2(11)
1(05)
1(05)
5(27)
3(16)
0(00)
2(11)
2(11)
1(05)
0
(00)
0(00)
1(05)
1(05)
2(11)
3(16)
0
(00)
9(50)
3(16)
2(11)
1(05)
1(05)
Two-sided
p
value
<
0.0001
0.049
ns
ns
0.063
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
"Activity
listed
as
abnormal
was
increased
activity
unless otherwise noted.
us.
However,
there
is a
growing body
of
literature sug-
gesting
a
connection between temporal lobe pathology
and
behavior abnormalities
(17,18).
Trimble (19)
re-
ports
that carbamazepine
is
frequently used
in
Europe
for
the
treatment
of
ADHD.
Silva
et al.
(20) also note
that carbamazepine
has
been
found
effective
in
treat-
ing
the
target
symptoms
of
ADHD
in a
review
of 10
studies,
3
double-blind studies
and 7
open trials.
Some clinicians have reservations about
the use
of
SPECT
in
children, feeling that
it may be
unsafe.
The
radiation exposure
from
SPECT
is
equivalent
to
a
pelvic X-ray (21). Nuclear medicine,
as a
specialty,
has
been doing studies
on
children
for
over
30
years
without
untoward
effects.
There
are
several limitations
to
this study.
The
ADHD
group
was
compared
to
psychiatric controls
as
opposed
to
normal controls. Normal subjects were
not
used
in
this study
due to the
small amounts
of
radiation exposure
for the
procedure. Even though
we
realized that this might cause some methodologi-
cal
concerns,
we
felt
that
the
information gained
us-
ing
a
matched control group would provide
useful
information.
Also,
the
studies were read
by
visual
in-
spection
as
opposed
to
absolute quantitative meas-
ures.
We
felt
that this method
of
reading
the
studies
had
more clinical value (this
is the way
nuclear phy-
sicians read scans),
but it
leaves room
for
physician
bias
and
interpretation,
as
opposed
to
more quanti-
tative
measures. More
research
is
needed
in
both
arenas (visual inspection
and
quantitative measures).
CONCLUSION
In
summary, this study
has
supported
the
find-
ings
of
other researchers regarding decreased pre-
frontal
activity
in
response
to an
intellectual challenge
in
children
and
adolescents
who
have ADHD.
Brain SPECT Imaging
in
ADHD
85
Fig.
1.
Attention deficit
hyperactivity
disorder.
ACKNOWLEDGMENT
This
study
was
supported,
in
part,
by a
grant
from
Amersham
Medi-Physics.
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... For example, ADHD and Major Depressive Disorder (MDD) are associated with distinct neurologic and emotional patterns. Results demonstrate that topologic response to GS is leading to decreased activity in the left hemisphere and could beneft ADHD challenges linked to increased left hemisphere activity in frontal and temporal regions during intellectual stress [139,140]. Further, MDD is associated with a decrease in Alpha symmetry [135,136]; Exposure to all GS shapes demonstrated Alpha symmetry, suggesting potential benefts for MDD rehabilitation. ...
... Furthermore, we posit that the fndings presented here in brainwave activity patterns, ANS and behavioral measurements, may suggest a novel approach for neurotrauma rehabilitation which could support benefts in desired plasticity. Importantly, Brain plasticity and Hebbian Learning [141] are crucial for neurotrauma rehabilitation [45,46,137] and are used in non-invasive practices such as brain-computer interface (BCI) and neurofeedback processes to model and ignite non-functional areas into activity [138,139]. Research found signifcant behavioral and structural impairments improvements post-neurotrauma and ADHD following such non-invasive approaches [101,142], further underscoring the role of plasticity in recovery [44][45][46]. Individuals recovering from neurotrauma, stemming from either Acquired Brain Injury (ABI) or Traumatic Brain Injury (TBI), frequently exhibit stressrelated emotional defcits, agitation and depressive symptoms [143][144][145]. ...
Effects of Geometric Sound on Brainwave Activity Patterns, Autonomic Nervous System Markers, Emotional Response, and Faraday Wave Pattern Morphology
Article
Full-text available
  • Mar 2024
  • EVID-BASED COMPL ALT
This study introduces Geometric Sound as a subfield of spatial sound featuring audio stimuli which are sonic holograms of mathematically defined 3D shapes. The effects of Geometric Sound on human physiology were investigated through EEG, heart rate, blood pressure, and a combination of questionnaires monitoring 50 healthy participants in two separate experiments. The impact of Geometric Sound on Faraday wave pattern morphology was further studied. The shapes examined, pyramid, cube, and sphere, exhibited varying significant effects on autonomic nervous system markers, brainwave power amplitude, topology, and connectivity patterns, in comparison to both the control (traditional stereo), and recorded baseline where no sound was presented. Brain activity in the Alpha band exhibited the most significant results, additional noteworthy results were observed across analysis paradigms in all frequency bands. Geometric Sound was found to significantly reduce heart rate and blood pressure and enhance relaxation and general well-being. Changes in EEG, heart rate, and blood pressure were primarily shape-dependent, and to a lesser extent sex-dependent. Pyramid Geometric Sound yielded the most significant results in most analysis paradigms. Faraday Waves patterns morphology analysis indicated that identical frequencies result in patterns that correlate with the excitation Geometric Sound shape. We suggest that Geometric Sound shows promise as a noninvasive therapeutic approach for physical and psychological conditions, stress-related disorders, depression, anxiety, and neurotrauma. Further research is warranted to elucidate underlying mechanisms and expand its applications.
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... However, in some studies, it was found a decrease in brain perfusion, especially in the prefrontal areas responsible for inhibition. 4,[30][31][32][33] The inability of the frontal region to fulfil this inhibition task is thought to play a role in ADHD patients. 32 Possibly inadequate inhibitory control causes exaggerated motor activity and unsuppressed hyperactivity in somatosensory areas. ...
... 4,[30][31][32][33] The inability of the frontal region to fulfil this inhibition task is thought to play a role in ADHD patients. 32 Possibly inadequate inhibitory control causes exaggerated motor activity and unsuppressed hyperactivity in somatosensory areas. As a result, increased brain metabolism and cardiac output increase cerebral venous return. ...
Superior Vena Cava Flow in Children With Attention Deficit Hyperactivity Disorder
Article
Full-text available
  • Sep 2023
Objective Attention deficit/hyperactivity disorder (ADHD), whose definition, diagnosis and treatment has been the subject of debate in the scientific community for a long time, is the most common neurobehavioral disorder in childhood. There are many studies on the pathophysiology of attention deficit. However, there is no study in the literature based on direct or indirect measurement of cerebral venous circulation in ADHD, and the effect of methylphenidate (MPH) treatment on cerebral venous circulation. Therefore, it was aimed to noninvasively measure superior vena cava (SVC) flow, which is an indirect indicator of cerebral venous flow, by transthoracic echocardiography in patients with ADHD. Methods In the study, 44 healthy children, and 40 ADHD patients who were planned to start on osmotic-release oral system (OROS)-MPH were included. SVC flows were measured in healthy children and before and after drug therapy of ADHD patients. Results SVC flow was found to be higher in ADHD patients compared to healthy children. A significant decrease was found in SVC flow of ADHD patients after OROS-MPH treatment. There was no decrease in SVC flow of patients who did not respond adequately to MPH treatment. Conclusion This first study of SVC flow in children with ADHD showed that ADHD was associated with increased SVC flow and MPH treatment had a reducing effect on this increased SVC flow. We believe that noninvasive, easily measurable, and reproducible SVC flow may be a new focus of interest for future comprehensive studies as a biomarker to support clinical evaluation in the diagnosis and treatment follow-up of ADHD patients.
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... 1 Meta-analysis studies have shown that ADHD children have a moderate weakness(.46-.69) in response inhibition, sustained attention, working memory, and planning ability. 2,3 They also have a high response time and unstable performance, showing executive attention(meta-attention) deficits [4][5][6] Neurophysiological studies have shown that their frontal lobe has lower activation during executive attention and planning tasks [7][8][9] In electrophysiological studies, ADHD children have higher delta-band and theta band activities, less beta-band activity in the central and frontal electrodes during eyes-open, eyes-closed resting, and cognitive activity tasks, suggesting lower activation of their cerebral cortex [10][11][12] Studies have also used the theta/beta power ratio(TBR) to represent the central nervous system's and cortex's arousal. 7,13 ADHD children have higher TBR, especially in the frontal area. ...
... The CON showed more TBR while doing the tasks, which might mean that the CON could not maintain the cortical arousal in the post-test. 7,13,19 The neuropsychological level results showed that WWNF could enhance sensory selection and attention control accuracy in the Go/No-Go subtests, increase cognitive flexibility by decreasing preservation errors, and increase concept formation and planning abilities. From the parents' view of behavioral symptoms and functions, WWNF training reduced ADHD symptoms, especially the large effect of inattention symptoms. ...
Effects of Twenty Hours of Neurofeedback-Based Neuropsychotherapy on the Executive Functions and Achievements among ADHD Children
Article
  • May 2022
Objective. Neurofeedback can reduce ADHD symptoms; however, current programs are relatively long, with fewer concerns about executive function (EF). The present study aimed to investigate a 20-hour combined computerized training neurofeedback program. Methods. Fifty ADHD children were randomly assigned to either the experimental group (EXP) or the wait-list control group (CON), who took training after the post-tests. The EF measures were the Tower of London (ToL), Wisconsin Card Sorting Test (WCST), and Comprehensive Nonverbal Attention Test (CNAT). SNAP-IV and questionnaires reported by parents constituted the behavioral measures. Two-way repeated-measures ANOVA and bootstrapping dependent t-tests were also used. Results. The F-tests revealed the interaction effects on ADHD symptoms and math scores. The EXP had increased the ToL scores, decreased the error and perseverative error rates on WCST, as well as the dysexecutive index on CNAT in the t-test. Conclusions. The training effects were related to behavioral symptoms and functions, EFs, and generalized achievement performances. We suggest that future studies could apply to different patients and examine the maintenance of the program.
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... The controlled clinical trials have been small with a range of 6-54 subjects (reviewed in Discussion). Our earliest study in this area included 54 children who met DSM-III-R criteria for ADHD compared to a clinical group of 18 children who did not meet those criteria (41). Visual, semi-quantitative reads revealed areas of increased perfusion in dorsal frontal cortices, while areas of decreased perfusion were noted in the orbitofrontal/inferior prefrontal cortices in baseline SPECT scans. ...
... Visual, semi-quantitative reads revealed areas of increased perfusion in dorsal frontal cortices, while areas of decreased perfusion were noted in the orbitofrontal/inferior prefrontal cortices in baseline SPECT scans. SPECT scans during intellectual challenge also revealed decreased inferior prefrontal cortical perfusion (41). A smaller study by our group in 27 older adults (>50 years) who met DSM-IV criteria for ADHD, but not for major depression, revealed a similar decrease of perfusion in the orbitofrontal cortices at baseline (42). ...
SPECT Functional Neuroimaging Distinguishes Adult Attention Deficit Hyperactivity Disorder From Healthy Controls in Big Data Imaging Cohorts
Article
Full-text available
  • Nov 2021
Background: The diagnosis of attention deficit hyperactivity disorder (ADHD) relies on history and observation, as no reliable biomarkers have been identified. In this study, we compared a large single diagnosis group of patients with ADHD (combined, inattentive, and hyperactive) to healthy controls using brain perfusion single-photon emission computed tomography (SPECT) imaging to determine specific brain regions which could serve as potential biomarkers to reliably distinguish ADHD. Methods: In a retrospective analysis, subjects (n = 1,135) were obtained from a large multisite psychiatric database, where resting state (baseline) and on-task SPECT scans were obtained. Only baseline scans were analyzed in the present study. Subjects were separated into two groups – Group 1 (n = 1,006) was composed of patients who only met criteria for ADHD with no comorbid diagnoses, while a control group (n = 129) composed of individuals who did not meet criteria for any psychiatric diagnosis, brain injury, or substance use served as a non-matched control. SPECT regions of interests (ROIs) and visual readings were analyzed using binary logistic regression. Predicted probabilities from this analysis were inputted into a Receiver Operating Characteristic analysis to identify sensitivity, specificity, and accuracy. Results: The baseline ROIs and visual readings show significant separations from healthy controls. Sensitivity of the visual reads was 100% while specificity was >97%. The sensitivity and specificity of the post-hoc ROI analysis were both 100%. Decreased perfusion was primarily seen in the orbitofrontal cortices, anterior cingulate gyri, areas of the prefrontal cortices, basal ganglia, and temporal lobes. In addition, ROI analysis revealed some unexpected areas with predictive value in distinguishing ADHD, such as cerebellar subregions and portions of the temporal lobes. Conclusions: Brain perfusion SPECT distinguishes adult ADHD patients without comorbidities from healthy controls. Areas which were highly significantly different from control and thus may serve as biomarkers in baseline SPECT scans included: medial anterior prefrontal cortex, left anterior temporal lobe, and right insular cortex. Future studies of these potential biomarkers in ADHD patients with comorbidities are warranted.
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... It is noteworthy to mention some evidence suggests that certain brain regions in individuals with ADHD may exhibit altered metabolism compared to typically developing controls. More precisely, single-photon emission computed tomography (SPECT) or positron emission tomography (PET) has documented decreased metabolic activity in the fronto-striatal regions among individuals diagnosed with ADHD [54][55][56][57]. Moreover, Lou et al. [58][59][60][61] have consistently identified reduced blood flow (hypoperfusion) in the striatal areas using SPECT, especially within the caudate nuclei region in ADHD children. ...
Alterations in Striatal Architecture and Biochemical Markers’ Levels During Postnatal Development in the Rat Model of an Attention Deficit/Hyperactivity Disorder (ADHD)
Article
Full-text available
Attention deficit/hyperactivity disorder (ADHD) is defined as a neurodevelopmental condition. The precise underlying mechanisms remain incompletely elucidated. A body of research suggests disruptions in both the cellular architecture and neuronal function within the brain regions of individuals with ADHD, coupled with disturbances in the biochemical parameters. This study seeks to evaluate the morphological characteristics with a volume measurement of the striatal regions and a neuron density assessment within the studied areas across different developmental stages in Spontaneously Hypertensive Rats (SHRs) and Wistar Kyoto Rats (WKYs). Furthermore, the investigation aims to scrutinize the levels and activities of specific markers related to immune function, oxidative stress, and metabolism within the striatum of juvenile and maturing SHRs compared to WKYs. The findings reveal that the most pronounced reductions in striatal volume occur during the juvenile stage in SHRs, alongside alterations in neuronal density within these brain regions compared to WKYs. Additionally, SHRs exhibit heightened levels and activities of various markers, including RAC-alpha serine/threonine-protein kinase (AKT-1), glucocorticoid receptor (GCsRβ), malondialdehyde (MDA), sulfhydryl groups (-SH), glucose (G), iron (Fe), lactate dehydrogenase (LDH). alanine transaminase (ALT), and aspartate transaminase (AST). In summary, notable changes in striatal morphology and elevated levels of inflammatory, oxidative, and metabolic markers within the striatum may be linked to the disrupted brain development and maturation observed in ADHD.
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... In addition, an intelligence test can further clarify the strengths and weaknesses of the person, and intervention methods can be adapted to the present intelligence profile, especially since 50% of ADHD patients have noticeable executive dysfunctions [31,32]. To complete the diagnostic evaluation, medical and neurological examinations are necessary to assess the underlying brain activity and functioning [33]. ADHD may take different manifestations depending on the person's age, which can reflect differences in brain regulatory systems [34][35][36]. ...
Psychological Treatments for Hyperactivity and Impulsivity in Children with ADHD: A Narrative Review
Article
Full-text available
  • Sep 2023
Treatment of the ADHD types (hyperactive-impulsive, inattentive, and combined) in children has rarely been studied separately, although their prognostic courses differ widely. In addition, data show that improvements in hyperactivity/impulsivity are hard to achieve. Thus, we focused on treatments tailored to hyperactivity/impulsivity. We examined meta-analyses and systematic reviews within the inter- and intra-individual treatments and found that psychoeducation and training for parents, school-based interventions, reinforcement strategies, and neurofeedback consistently showed small to moderate effect sizes in reducing hyperactivity/impulsivity in children. Conversely, emotional self-regulation, social skills, and cognitive trainings showed unsatisfactory results. In summary, we found that the quality of usual care can be surpassed when the designated interventions are purposefully combined into a multimodal treatment program.
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... Especially, as 50% of ADHD patients have noticeable executive dysfunctions [43,44]. To complete the diagnostic evaluation, medical and neurological examinations are necessary to assess the underlying brain activity and functioning [45]. 5 ...
Psychological Treatments for Hyperactivity and Impulsivity in Children with ADHD: A Narrative Review
Preprint
Full-text available
  • Aug 2023
Treatment of the ADHD types (hyperactive-impulsive, inattentive, and combined) in children has rarely been studied separately, although their prognostic courses differ widely. In addition, data show that improvements in hyperactivity/impulsivity are hard to achieve. Thus, we focused on treatments tailored for hyperactivity/impulsivity. We examined meta-analyses and systematic reviews within the inter- and intra-individual treatments and found that psychoeducation and training for parents, school-based interventions, reinforcement strategies, and neurofeedback consistently showed small to moderate effect sizes in reducing hyperactivity/impulsivity in children. Conversely, emotional self-regulation, social skills, and cognitive trainings showed unsatisfactory results. In summary, we found that the quality of usual care can be surpassed when the designated interventions are purposefully combined into a multimodal treatment program.
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... According to previous literature, these areas are among the most involved in ADHD disturb [26]. The frontal cortex is related to attention mechanisms and organization [26], [27] suggests that this area is impaired in subjects affected by ADHD. Conversely, the limbic system, cerebellum, and basal ganglia are associated with behavior, emotions, and impulsivity. ...
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Near‐infrared spectroscopy in child and adolescent neurodevelopmental disorders
Article
Full-text available
  • Nov 2022
Near‐infrared spectroscopy (NIRS) is a noninvasive optical technique that uses the near‐infrared spectrum for functional neuroimaging by measuring oxygenation and hemodynamic changes in the cerebral cortex. The advantages of NIRS include its portability and ease of application, which allows for testing with the subject in natural positions, such as sitting or standing. Since 1994, NIRS has been increasingly used to conduct functional activation studies on different psychiatric disorders, most prominently schizophrenia, depression, bipolar disorder, and neurodevelopmental disorders. However, limited information on its use among child and adolescent patients is available. We herein review recent findings obtained using NIRS measurements of the brain during cognitive tasks in neurodevelopmental disorders, such as autism spectrum disorder, attention‐deficit/hyperactivity disorder, obsessive–compulsive disorder, and Tourette's disorder. This will facilitate evaluations of the causation and treatment of prefrontal cortex dysfunctions.
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Neuroactivation and Neuroimaging with SPET
Book
Full-text available
  • Jan 1991
This book describes the application of single photon emission tomography (SPET) to neuroactivation imaging in particular and neuroimaging in general. Protocols for SPET, neuroactivation and neuroimaging are described in detail and results are given and discussed on the basis of clinical material and case histories. Normal functional anatomy is correlated with data from MRI. High resolution cerebral blood flow (CBF) imaging is described with the use of SPET technology. Split dose CBF imaging is also mentioned, for activation studies in a variety of normal and diseased states which include the dementias (AIDS, Alzheimer's disease and multi-infarction dementia), cerebrovascular disease, depression, schizophrenia, obsessive compulsive disorders, movement disorders (Parkinson's disease, Gilles de la Tourette syndrome, Huntingdon's chorea, Sydenham's chorea), epilepsy and tumours. Examples of motor, frontal and visual activation studies are also given.
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Changes in regional cerebral blood flow during brain maturation in children and adolescents
Article
Full-text available
  • Jun 1992
Regional cerebral blood flow (rCBF) was studied by SPECT using 133Xe in 42 children, aged 2 days to 19 years, considered as neurologically normal. rCBF was measured on cortical regions and on the cerebellum and thalamus. Curves for reference values and standard deviation were defined for each region. At birth, cortical rCBFs were lower than those for adults; after birth they increased until 5 or 6 yr of age to values 50%-85% higher than those for adults and thereafter decreased, reaching adult levels between 15 and 19 yr. Neonatal values of rCBF on cerebellum and thalamus were slightly higher than adult level, but not significantly; after age 1, they followed the common pattern for cortical curves. When rCBFs were expressed in percent global CBF, they were lower at birth than adult levels in the cortex, then increased and reached a plateau corresponding to the adult value before the second year of age. The time needed to reach normal adult values differed for each cortical region. The shortest time was found on the primary cortex and the longest on the associative cortex. Cognitive development of the child seems to be related to changes in blood flow of the corresponding brain regions.
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SPECT Functional Brain Imaging
Chapter
  • Dec 2002
This chapter provides an overview of the technical aspects of single-photon-emission computed tomography (SPECT) functional brain imaging, referring primarily to the most common SPECT brain function measure, regional cerebral blood flow (rCBF). SPECT images of rCBF are influenced by a number of factors separate from pathology, including the quality of the tomographic device; the radiopharmaceutical employed; environmental conditions at the time of radiotracer administration; characteristics of the subject such as age, gender, and handedness the format used for image presentation; and image processing techniques. SPECT instruments fall into two categories: non-camera-based and camera-based systems. Non-camera-based systems include rotating detector arrays, multidetector scanners, and fixed rings. Both single-head and multihead gamma-camera-based systems are vastly more prevalent than dedicated tomographs, primarily because they can do both head and body SPECT. Modern single-head tomographs have overcome many of the limitations of the original systems, such as poor head alignment, magnetic field aberrations, and inadequate uniformity and linearity for tomography. Several 99mTc-labeled and 123I-labeled radiopharmaceuticals for the SPECT measurement of rCBF have been developed. It is also possible to measure regional cerebral blood volume (rCBV) using SPECT techniques. Receptor imaging with SPECT is still primarily a research tool, although at least one agent for D2 receptor studies and one agent for dopamine and serotonin transporter imaging are commercially available.
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Correlation Between Regional Cerebral Blood Flow and Oxidative Metabolism
Article
  • Aug 1976
  • ARCH NEUROL-CHICAGO
• To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.
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Correlation between regional cerebral blood flow and oxidative metabolism. In vivo studies in man
Article
  • Sep 1976
  • ARCH NEUROL-CHICAGO
To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.
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Quantitative analysis of EEG in boys with attention-deficit-hyperactivity disorder: Controlled study with clinical implications
Article
  • Feb 1992
  • PEDIATR NEUROL
Sixteen-channel topographic brain mapping of electroencephalograms of 25 right-handed males, 9-12 years of age, with attention-deficit-hyperactivity disorder revealed increased theta (4-7.75 Hz) and decreased beta 1 (12.75-21 Hz) when compared with 27 controls matched for age and grade level. The differences were greater when patients were tested for reading and drawing skills, but were decreased when they were at rest during visual fixation. Although the differences in patients with attention-deficit-hyperactivity disorder were generalized, increased theta was more prominent in frontal regions, while beta 1 was significantly decreased in temporal regions. Principal component analysis was used to combine the variables into 2 components which accounted for 82% of the total variance. A discriminant function analysis using these components was able to predict group membership for attention-deficit-hyperactivity disorder patients 80% of the time and 74% for controls. These findings support the use of topographic electroencephalography for further elucidation of the neurophysiology of attention-deficit-hyperactivity disorder.
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Discourse on the development of EEG diagnostics and biofeedback for attention-deficit/hyperactivity disorders
Article
  • Oct 1991
  • Biofeedback Self Regul
This article presents a review of work that my colleagues and I have been doing during the past 15 years developing a rationale for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) and treatment of ADHD employing EEG biofeedback techniques. The article first briefly reviews the history of research and theory for understanding ADHD and then deals with the development of EEG and event-related potential (ERP) assessment paradigms and treatment protocols for this disorder, including our work and that of others who have replicated our results. Illustrative material from our current research and child case studies is included. Suggestions for future experimental and clinical work in this area are presented and theoretical issues involving the understanding of the neurophysiological and neurological basis of ADHD are discussed.
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