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Keywords:
ACPT, attention-deficit hyperactivity disorder, P300, Stroop, Wisconsin card sorting test
Egypt J Psychiatr 42:139–147
© 2021 Egyptian Journal of Psychiatry
1110-1105
© 2021 Egyptian Journal of Psychiatry | Published by Wolters Kluwer - Medknow DOI: 10.4103/ejpsy.ejpsy_12_21
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Continuous Performance Test and cortical auditory efficacy, and that P300 amplitude is related to
evoked potentials (CAEPs) are computerized tests response to atomoxetine, whereas the P300 latency
developed to measure selected EF skills in children reflects the processing speed of stimulus
(Marquardt et al., 2018). discrimination.
Throughout the previous 20 years, the psychotic This work aims to assess CAEPs as well as P300 in
diseases’ biological substrates were investigated children with ADHD, and its correlation with
using electrophysiology. The advantage of neurocognitive tests [Wisconsin card sorting test
electrophysiological procedures is the ability to scan (WCST), digit span (DS), Stroop test (ST)].
mental processes in real time without invasion.
Moreover, fast neural actions and oscillations with
high frequency are captured by their extremely high Patients and methods
time resolution, and this makes scanning of functional This cross-sectional prospective study was conducted on
brain possible through source analysis of maps of high 103 children, who were divided into two groups: first
density (Blakey et al., 2018). group was 53 children with ADHD (18 females and 35
males) newly diagnosed with ADHD, who were drug-
In the few years, the processing of information and naïve children, aged between 8 and 14 years. The
neurological states assessment will be performed ADHD diagnosis was according to the Diagnostic and
mainly using electrophysiological methods, which are statistical manual of mental disorders, 5th ed.. They were
promising methods for assessment of causes and matched with 50 normal controls (29 female and 21
predictors of response to clinical treatment male) with normal hearing, with no history of attention
(Kamarajan and Porjesz, 2015). deficit or hyperactivity, with normal school performance
and matched with patients for age, sex, educational and
In ADHD cases, changed event-related potential (ERP) social level, and intelligence quotient (IQ).
has been noted, which reflects neurocognitive
dysfunction related to attention domains, inhibitory All attendants of the outpatient child and adolescent
control, and processing of reward and data. As a result psychiatry clinic in a Psychiatry and Neurology Center
of ERP findings, different stages of sensory and cognitive were recruited. The study was conducted in the
functions have been shown to be processed in a different Department of Neuropsychiatry and Department of
manner in children experiencing ADHD. In addition, a Audiovestibular Medicine Units, Tanta University
different form of component of ERP was observed Hospitals.
between subtypes of ADHD. ERP component was
used as a predictor for treatment response (Marquardt The idea of the research was explained in detail to the
et al., 2018). participants. Patients who agreed to participate signed an
informed consent. The participation was voluntary, and
Auditory P300 is a positive ERP component the patients could refuse to continue the study at any time
happening nearly 300 ms following target stimuli. It without penalty or loss of advantages. Every patient had a
is a selective attention neurological and physiological code number. Results of this research were used only for
correlate, working memory, and novelty detection. The scientific purpose. The duration of the study ranged from
P300 is a late ERP component that has been suggested 6 months, in the period from March 2018 to September
to assess functions of execution and attention, 2018. The trial has an approval from the medical ethical
including the function of the memory of working, committees of Faculty of Medicine, Tanta University.
classifying of event, attentional resource allocation, An informed consent was taken from the caregivers of all
and attentional reorientation (Polich, 2007). participants.
(1) Children with mental retardation. P300 and CAEPs were recorded from both control and
(2) Children with hearing loss or ear disease that study groups by Smart EPs of intelligent hearing system.
affects the hearing function. Regarding P300, it was recorded in the oddball paradigm
(3) Children with serious neurological, psychiatric, or using two kinds of stimuli (speech and tone) that were
metabolic disorders that affect cognitive and EFs. presented in two paradigms. In the first paradigm,
1000 Hz and 2000 Hz were utilized as the standard
All the participants were subjected to the following: and deviant stimuli simultaneously, whereas in the
second paradigm, /ga/ stimuli were used as a standard
(1) Detailed psychiatric history from parents or stimulus and /da/ stimuli were utilized as the deviant
caregiver. stimulus using Smart EPs of Intelligent hearing system.
(2) Assessment of IQ: Wechsler intelligence scale for
children (WICS) to measure IQ. The two stimuli types were presented at one second
(3) A semi-structured interview in the form of Kiddie rate of repetition, 15% deviant probability, and at 50
Schedule of affective disorders and schizophrenia- dBSL (re PTA average at 500, 1000, 2000, and
present and life time version to confirm the 4000 Hz) monaurally to each ear in the two groups
diagnosis of ADHD. via an insert-phone. Four electrodes were used to
(4) Conners’ parent/teacher rating scale abbreviated record P300, which placed at Fz (?ve electrode), Fpz
form for ADHD symptoms. (ground electrode), and M1 and M2 (mastoids) as
(5) Neuropsychological tests measuring EFs (WCST reference electrodes according to side of stimulation.
and Stroop). The child was asked to count the deviant one /da/.
(6) Basic audiological assessment, including P300 was identified as the most robust positive wave
audiometry of pure tone and audiometry of around 300 ms following N1-P2 complex, and both
speech using a GSI 61 audiometer. absolute latency and amplitude were measured.
(7) Immittance test using interacoustic.
(8) Sustained attention test using auditory continuous CAEPs components were recorded using Speech
performance test (ACPT). stimuli CV syllable /da/ using the same electrode
(9) Electrophysiological test both CAEPs using tone montage for P300. The settings of filter (recording
and speech stimuli and P300 testing using oddball bandwidth) were 1–30 Hz (low pass 30 Hz and high
paradigm. pass 1 Hz). Stimuli have been monaurally presented
to both ears via an ER3A insert phone beginning with
The participants of the study were recruited from child ear of right side. The stimulus was presented at 90
and adolescent psychiatric outpatient by the first and dBnHL. All patients and their parents were informed
last investigators. Detailed psychiatric history was of the test procedure.
taken from the parents or the caregiver of children,
with clinical evaluation of ADHD according to During acquisition of the test, each patient was informed
Diagnostic and statistical manual of mental disorders, to be calm and lie down on a comfortable coach. They
5th ed., and then Kiddie Schedule of affective were advised at the same time not to focus on the
disorders and schizophrenia-present and life time presented stimuli. For identification of the response,
version was applied to ensure diagnosis and exclude the response consisted of a positive wave at about
any psychiatric comorbidity. IQ was evaluated by a 50 ms (P1), a large negative wave at about 80–100 ms
trained psychologist, and Conners’ parent rating scale (N1), and a subsequent positive wave at about
was completed, and then the children who fulfilled the 180–200 ms (P2). Classically, the N2 is a negativity
inclusion criteria of the research were referred to following the P2. Calculation of the latency and
Audiovestibular Medicine Unit to be assessed the amplitude (peak to peak or baseline to peak) of each
second and third investigator, for P300 and CAEPs. wave was done as follows: the P1-N1-P2 latency, which
was the time from stimulus onset to the first positivity
Then the cases and control were referred back to (P1), first negativity (N1), a subsequent positive wave at
neuropsychiatry department for further assessment of about 180–200 ms (P2), and a second negativity (N2).
their EF in a separate session. The computerized version The P1-N1-P2 amplitude that was usually measured
of WCST was applied for all participants by the first from the trace’s zero voltage to the most positive or
instigator, whereas computerized ST was applied by the negative trough in that trace.
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DS backward, which reflects working memory, P300 in response to speech stimuli using oddball
was significantly different among clinical group and paradigm was recorded for both groups; both P300
control group. ADHD group could repeat fewer absolute latency and amplitude were measured. P300
digits backward than the control group (P<0.05) absolute latency showed delay in ADHD in
(Table 2). comparison with the control group. This delay was
statistically significant, as shown in Table 3. Regarding
ST, the time needed to name the color of the word, was P300 amplitude, statistically significant differences
significantly different among children with ADHD were found between the two groups (Table 3).
compared with the normal control, as children with
ADHD needed more time to read the name of the CAEP components were recorded using da stimuli.
color (P<0.05) (Table 2). Regarding wave detectability, all CAEP waves
Table 3 Results of P300 and cortical auditory evoked potential latency and amplitude using both speech and tone stimuli as well
as ACPT among study and control groups
Groups
ADHD (N=53) Control (N=50) Test statistic P value
Speech
P300 latency
Mean 371.28 328.52 13.94 <0.001*
SD 13.00 17.62
P300 amplitude
Mean 1.82 3.25 17.38 <0.001*
SD 0.47 0.36
Latency
P1
Mean 101.1 60.5 8.56 <0.001*
SD 33.1 9.5
N1
Mean 176.5 108.7 9.75 <0.001*
SD 47.5 17.1
P2
Mean 232.2 184.3 6.15 <0.001*
SD 50.7 24.4
N2
Median 320.0 233.0 7.44 <0.001*
IQR 280.0–340.0 210.0–246.0
Mean rank 73.27 29.45
Amplitude
P1
Median 1.66 3.65 3.67 <0.001*
IQR 1.52–3.00 2.10–6.00
Mean rank 41.51 63.12
N1
Mean 5.19 6.06 1.14 0.254
SD 3.56 4.10
P2
Median 1.99 5.75 6.33 <0.001*
IQR 1.24–2.11 2.30–10.10
Mean rank 33.91 71.18
N2
Median 1.68 5.83 7.11 <0.001*
IQR 1.30–3.85 4.00–9.01
Mean rank 31.68 73.54
ACPT
Mean 74.9 96.9 16.67 <0.001*
SD 9.1 2.9
ACPT, auditory continuous performance test; ADHD, attention-deficit hyperactivity disorder; IQR, interquartile range. *Significant at P value
less than 0.05.
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(P1N1P2N2) were 100% detectable for both groups. Conners’ parent rating scale for ADHD symptoms was
Regarding wave latency, all CAEP components used in this study. A score higher than 15 reflects
presented delayed latencies of significance in ADHD presence of ADHD, and higher score reflects severity
in comparison with the control group. Different of ADHD. There was a significant statistical difference
amplitude components of CAEP were measured in between ADHD group and control group.
the two groups, with difference of statistical
significance for P1-N1 amplitude. On the contrary, WCST was used as an indicator of set shifting,
a nonsignificant relation was found among both study cognitive flexibility, solving of problem, feedback
groups regarding P2-N2 amplitude (Table 3). using, the ability to alter wrong strategies, and to
prevent arrogant responses.
Auditory continuous performance test was recorded for
both groups, and there was a significant difference Perseverative responses (replies in the new group that
between both groups, with higher percentage in the were classified per the previous classification principle),
control group (Table 3). perseverative errors (wrongly classified cards, classified
per the previous classification principle), and failure to
A correlation test was done between maintain set parameters of WCST were used as
electrophysiological tests results and the tests of variables in our study. We selected these parameters
cognitive functions for ADHD group. A positive especially, as most of the studies on WCST had used
correlation was present between P300 amplitude and same parameters in the test assessment, especially
WCST (perseverative errors) (P=0.03). Moreover, a preservative responses, which is considered a
positive correlation was present among P300 amplitude sensitive parameter in test assessment.
and ST results (P=0.01)
WCST can differentiate children with ADHD from
There was also a positive correlation between N2 latency normal control. When the child had higher scores than
and DS backward (P=0.03). A positive correlation control, this reflects impairment of set shifting and
was present among N1 amplitude results and cognitive flexibility components of EFs (Heaton and
Conners’ parent rating scale results (P=0.04) (Table 4). Staff, 1993).
Table 4 Correlation of P300, cortical auditory evoked potential latency and amplitude as well as ACPT with cognitive functions in
the studied patients (N=53)
IQ ADHD WCST (PR) WCST (PE) WCST (FMS) DSB Stroop
r P r P r P r P R P r P r P
P300 latency −0.18 0.20 0.01 0.50 0.0 0.99 −0.02 0.99 −0.04 0.77 0.11 0.42 0.09 0.58
P300 amplitude −0.23 0.10 0.08 0.57 0.08 0.58 0.30 0.03* −0.04 0.76 0.26 0.06 0.34 0.01*
P1 latency 0.22 0.12 0.24 0.09 0.12 0.41 −0.01 0.50 −0.05 0.74 0.04 0.76 0.12 0.39
N1 latency 0.22 0.12 0.25 0.07 0.14 0.33 0.08 0.96 −0.07 0.62 0.07 0.62 0.18 0.20
P2 latency 0.13 0.36 0.22 0.11 0.05 0.72 −0.09 0.55 −0.05 0.73 0.18 0.19 0.19 0.17
N2 latency 0.05 0.74 0.17 0.22 0.22 0.11 0.08 0.58 0.01 0.97 0.31 0.03* 0.12 0.41
P1 amplitude 0.07 0.60 0.24 0.09 0.03 0.85 0.12 0.39 0.03 0.85 0.13 0.36 0.12 0.39
N1 amplitude −0.06 0.17 0.28 0.04* 0.04 0.79 0.13 0.35 −0.03 0.86 0.22 0.11 0.23 0.09
P2 amplitude 0.10 0.46 0.12 0.39 0.02 0.87 −0.02 0.91 −0.05 0.72 0.11 0.42 0.02 0.87
N2 amplitude 0.02 0.91 −0.04 0.76 0.02 0.08 0.14 0.31 −0.15 0.29 0.07 0.65 0.03 0.85
ACPT −0.12 0.40 0.09 0.51 0.02 0.90 0.10 0.46 0.27 0.05 0.26 0.06 0.19 0.17
ACPT, auditory continuous performance test; ADHD, attention-deficit hyperactivity disorder; DSB, digit span backward; FMS, failure to
maintain set parameter; IQ, intelligence quotient; PE, perseverative error; PR, perseverative response; r, correlation coefficient; WCST,
Wisconsin card sorting test. *Significant at P value less than 0.05.
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When we try to connect results in our work with the This leads to working memory disruptions and
pathophysiology of ADHD, there is a relation between interferes with planning and organized behavioral
set shifting component of EFs and the impairment patterns.
in the left dorsolateral prefrontal cortex, so this test
(WCST) may have a role in evaluation the underlying Our results were in concordance with the study
impairment in ADHD. carried out by MacLeod (1991), who implied
that an inhibitory control deficit is a key deficit in
In this study, our results were in concordance with ADHD, which is important in situations required
Sergeant et al. (2002), who stated that many WCST withholding or sudden interruption of an ongoing
trials could differentiate ADHD from normal cases, action. Our work was also in concordance with Harris
but these conclusions depend on which parameters et al. (1995).
have been used. In most of the studies, perseverative
response (which is considered a sensitive parameter in This test was used for assessment of working memory.
WCST), perseverative faults, and inability to preserve It was found that children with ADHD could recall
set were used to differentiate between ADHD and fewer digits than the control, so there was a significant
normal controls. difference from control, which denotes working
memory impairment in our sample of ADHD.
Our study is in concordance with other many studies
that found set shifting impairment in patients with Working memory impairment in children with
ADHD in comparison with normal control, for ADHD can be manifested in many occasions, as
example, the studies of Barkley et al. (1992), Carter these children can find great difficulty in
et al. (1995), Houghton et al. (1999), Seidman et al. remembering where they just put something, what
(2000), Weyandt and Willis (1994), and Zakzanis et al. someone just said to them, what they have just read,
(2005). or what they are about to say. There was also a positive
correlation between N2 latency and DS backward.
In this study, a positive correlation was present among
P300 amplitude and WCST (perseverative errors), A study of Barnett et al. (2001) agreed with the current
which is a very important physiological correlate. results. They found working memory deficit in patients
with ADHD in comparison with normal controls. Our
Scheres et al. (2003) results were not in concordance trial was also in concordance with many other studies
with our results, as they found that perseverative errors such as that of Willcutt et al. (2005) and that of
and failure to maintain set did a poor job in Martinussen et al. (2005) and Finke et al. (2006).
discriminating between ADHD and normal control.
In our study, we measured the P300 absolute latency
ST was used in our study to detect the executive and amplitude in response to speech stimuli using
inhibition. Our ADHD sample was significantly oddball paradigm in both groups. P300 absolute
impaired relative to control group in the test. latency showed statistically significant delay in
ADHD in comparison with the control group.
Moreover, a positive correlation was present among Regarding the P300 amplitude, a reduction of
P300 amplitude and ST results. It is a neurological and statistically significance was present in children with
physiological correlate of selective attention, working ADHD.
memory, and novelty detection. The P300 is a late
ERP component and was suggested to identify Our results agreed with Borja and Ponde (2009), Tsai
executive and attentional functions, including the et al. (2012), and Yamamuro et al. (2016). who reported
function of the working memory, categorizations of P300 latency time increased, and in individuals with
events, attentional resource allocation, and attentional ADHD, the amplitude decreased (Borja and Ponde,
reorientation (Polich, 2007). 2009; Yamamuro et al., 2016).
Poor inhibition is manifested in many situations in In the ADHD, it is noted that the P300 amplitude
children with ADHD who are impulsive as these decrease represents deficits in the task-relevant
children find difficulty in waiting turn, interrupt and processing or salient data, selective attention, and
intrude others, and often blurt out responses before context updating, whereas the delayed P300 latency
the completion of questions. Inhibitory control of the was explained by slower processing in ADHD cases
deficit can encroach into capacity of working memory. (Mercugliano, 1999).
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On the contrary, some trials did not agree with our processing. The N1 decreased in ADHD suggested
results. Romero et al. (2013) made a comparison decreased automatic attention to salient sound stimuli,
between the performance in children with and which might be owing to decreased activity of the
without ADHD. In comparison with the control pathways of brain-stem arousal (Sable et al., 2013).
group, normal values of P300 latency and amplitude
in the ADHD group were noted (Romero et al., 2013). Wang et al. (2008) stated that the frontal cortex could
be an integrated component of an inhibitory circuit
They explained these nonsignificant differences in that inhibits the response to irrelevant, unattended
their study that the sample was small and stimuli by feeding back on sensory areas (in a
recommend a higher number of cases to better normally functioning brain). This sensory filtering is
auditory pathway analysis. One other possible reason reflected in reduced N1 amplitudes, indicating reduced
for them was that children with ADHD have attention to those sounds. Low-amplitude N1 may
modifications in their processes of preattention and reflect reduced activity in the hindbrain
discrimination; nevertheless, through the interaction of norepinephrine system, including the locus coeruleus
brain plasticity and reconfiguration of nerve cells, these (Halperin and Schulz, 2006).
children may process the data via other structures of the
central nervous system. The N2 has been associated with cognitive control and
response inhibition. Sable et al. (2013) studied
CAEP waves include P1, N1, P2, and N2; they provide automatic attention in young adults with ADHD.
information about perception of sound by the auditory Their results showed reduced N1 amplitude and
cortex. P1 is a positive wave at 50–100 ms after increased N2 in patients with ADHD, and they
stimulus and N1 is a negative peak that occurs at suggested that those patients may have developed
∼80–120 ms following the stimulus initiation. certain compensatory top–down attentional
Latencies of P1 and N1 are a helpful screening tool mechanisms. This may explain the nonsignificance
of central auditory development. P2 is a second positive in the N2 amplitude between the both groups in our
peak at ∼100–160 ms following stimulus and N2 study. However, some studies showed reduced N2
latency was about 200–280 ms (Durante et al., 2014; peak in ADHD compared with the control group, and
Sharma et al., 2015). they suggested that this may indicate an atypical
frontal inhibition process in ADHD (Barry et al.,
CAEP components obtained from speech stimuli 2003).
provide information referring to detection of speech
stimuli and processing in the auditory cortex (Souza The P2 component was suggested to reflect automatic
and Tremblay, 2006). stimulus discrimination and the inhibition of further
processing of competing (Oades, 1998).
In our study, CAEP was recorded using da stimuli.
Regarding wave detectability, all CAEP waves (P1, Romero et al. (2013) stated that N2 latency was delayed
N1, P2, and N2) were 100% detectable for both in ADHD, and they explained it by the decrease in the
groups. Children with ADHD had delay in latencies responses efficiency involving processes of preattention
by all CAEP components which was significant in and discrimination.
comparison with controls. The amplitudes of different
C components were evaluated in the two groups, with Auditory continuous performance test was used in
a statistically significant decrease in the amplitudes of cases with ADHD to study sustained attention in
P1, N1, and P2. those patients. The performance of children and
adults with ADHD was found to be worse
In ADHD, processes of response inhibition are affected compared with the control group in many studies
by concurrent data owing to high distractibility, and this (Doehnert et al., 2013). In our study, there was a
is reflected in the reduction in the amplitude of both P1 statistically significant difference between ADHD
and N1. This might be represented in processes of and the control group, with higher percentage in the
perceptual gating and bottom-up attentional selection controls. Distractibility, hyperactivity, and impulsivity
(P1 and N1) and at the resource allocation level (P2) are the main hallmarks in ADHD (Vahia, 2013). The
(Herrmann and Knight, 2001). efficiency of information processing and the ability to
stay focused on a monotonous task are deficient in
Auditory P1 and N1 is used to assess automatic patients with ADHD, and they have poor performance
attention, and it reflects the sensory stimuli on sustained attention (Mazor-Karsenty et al., 2019).
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