ADHD Electrophysiological Subtypes and Implications in Transcranial Direct-current Stimulation

Implications of Electrophysiological ADHD Endophenotypes to Predict Response to Transcranial Direct-Current Stimulation

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01649232

Acronym

tdcs&adhd

Enrollment

Registered

2012-07-25

Start date

2012-06-30

Completion date

2012-12-31

Last updated

2024-05-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

ADD, ADHD

Keywords

tdcs, tms, qeeg, neuroplasticity, brain networks, add, adhs

Brief summary

In the present study the aim is to examine whether transcranial direct-current stimulation (tDCS) generated excitability changes and induce modifications of functional cortical architecture in Attention Deficit Hyperactivity Disorder (ADHD) patients. To achieve this, the investigators used an event-related potential (ERP) analysis based on 20 channel EEG recordings in ADHD subjects before and after bipolar tDCS-anode stimulation over F3/F4 or T5/T6 or P4/P3, during resting state and measure clinical scores and visual CPT tasks changes. Time courses and topography of independent component visual ERPs were compared before and after tDCS.

Detailed description

Important advances in the understanding of ADHD pathophysiology, such fMRI studies showing a focal frontotemporal loops dysfunction in brain activity, suggest that frontal brain stimulation might be helpful for the treatment of ADHD. In a recent study of Lyon's university with tDCS they concluded that tDCS is cheaper and easier-use than transcranial magnetic stimulation (TMS) and the impact on symptomatology seems larger (impact on negative symptoms of schizophrenic patients) and longer (at least 3 months duration) than that TMS currently permits. It is possible that tDCS could in the future be used at home by patients themselves. The efficacy of tDCS depends of parameters like electrode position and current strength. In this trial, The investigators investigated the effects of 12 days of anodal stimulation of the left dorsolateral prefrontal cortex in ten patients with ADHD (aged 8 +/- 3 years). tDCS was applied through a saline-soaked pair of surface sponge electrodes (35 cm2). The anode electrode was placed over F3/F4 or T5/T6 or P4/P3(based on the 10-20 International EEG System) of each subject. The cathode was placed over the contralateral mastoid area. A constant current between 1.1 and 2.0 mA was applied for 25 min/day (administered for 12 alternated days). Prior to the first session, ADHD subjects were asked to complete and return a series of questionnaires, including the Conners Brief Symptom Inventory, a health history questionnaire, and the QEEG questionnaire. Subjects were then tested in a first session which lasted approximately three hours. During this period, a comprehensive structured clinical interview was carried out, comprising of an assessment of current and past ADHD symptoms, the history of problems at school, the past psychiatric history (including drug and medication use), as well as past and present comorbidities. Subsequently, EEG data was acquired. EEG data was first recorded while the subject was in eyes-closed and eyes-open resting conditions, lasting four minutes each. Then data was recorded while subjects performed a visual continuous performance task (VCPT). The VCPT took approximately 22 minutes to complete. In addition, subjects randomly performed either an auditory or an emotional continuous performance task. The control group had a shortened procedure. Subjects were tested in a single session lasting approximately two and a half hours. During this period, a series of questionnaires (Brief Symptom Inventory, Health History questionnaire, Current Symptoms Scales) were filled out and thereafter, EEG data was acquired. Subsequently, a working memory task, which is not relevant here, was administered. EEG was recorded using a Mitsar 201 19-channel electroencephalographic system. The input signals referenced to the linked ears were filtered between 0.5 and 50 Hz and digitized at a sampling rate of 250 Hz. Impedance was kept below 5 kOhm for all electrodes. Electrodes were placed according to the International 10-20 system using a electrode cap. Quantitative data was calculated using WinEEG software. Linked ears reference montage was changed to average reference montage prior to data processing. Eye-blink artefacts were corrected by zeroing the activation curves of individual ICA component score responding to eye blinks. In addition, epochs of the filtered electroencephalogram with excessive amplitude (\>100 μV) and/or excessive fast (\>35 μV in 20 to 35 Hz band) and slow (\>50 μV in 0 to 1 Hz band) activity were automatically marked and excluded from further analysis. Finally, EEG was manually inspected to verify artefact removal. Behavioral task The VCPT is a modification of the visual two-stimulus GO/NOGO paradigm. Three categories of visual stimuli were selected: 20 pictures of animals, 20 pictures of plants, and 20 pictures of humans (presented together with an artificial novel sound). The trials consisted of presentations of pairs of stimuli: animal-animal (GO trials), animal-plant (NOGO trials), plant-plant (IGNORE trials), and plant-human (NOVEL trials). The trials were grouped into four blocks. In each block a unique set of five animal stimuli, five plant stimuli and five human stimuli was selected. Each block consisted of a pseudo-random presentation of 100 stimuli pairs with equal probability for each trial category. The task was to press a button as fast as possible in response to GO trials. According to the task design, two preparatory sets were distinguished in the trials. In the Continue set a picture of an animal is presented as the first stimulus and the subject is supposed to prepare to respond. In the Discontinue set a picture of a plant is presented as the first stimulus and the subject does not need to prepare to respond. During the task, subjects were seated in a comfortable chair, 1.5 m in front of a computer screen. The stimuli were presented on a 17 inch monitor using the Psytask (Mitsar Ltd.) software. The primary outcome was change in score on the QEEG Rating Scale (AMEN questionnaire). The ERP and questionnaire/behavioural assessments will be made at baseline (before stimulation)and 3 months after stimulation. This study involved 30 subjects, all aged between 7 and 13. All have been diagnosed with ADHD by a medical professional.

Interventions

DEVICEActive tDCS

tDCS applied to left dorsolateral prefrontal scalp area through a saline-soaked pair of surface sponge electrodes (35 cm2). The anode electrode was placed over F3 (based on the 10-20 International EEG System) of each subject. The cathode was placed over the contralateral mastoid area. A constant current of 1.1 mA was applied for 25 min/day (administered for 12 alternated days).

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

8 Years to 68 Years

Healthy volunteers

Yes

Inclusion criteria

1. ADHD diagnosis. 2. Age between 7 and 65 years. 3. Comorbidities were no reason for subject exclusion.

Exclusion criteria

1. Presence of psychosis. 2. Subjects taking medication,they had refrained from taking methylphenidate during 24 hours before testing. 3. Subjects taking other psychotropics were not included in the study. 4. Subjects which had suffered of a head injury with subsequent loss of consciousness, and subjects suffering from neurological or systemic medical diseases were excluded from the study.

Design outcomes

Primary

Measure	Time frame	Description
Clinical Assessment (Amen Questionnaire)	From September to December 2012	The Amen Attention Deficit Disorder (ADD) Type Questionnaire is a 71-question self-test that evaluates the ADD syndrome. 0 never, 1 rarely, 2 Occasionally, 3 Often and 4 Very Often. Consists of a series of questions that evaluate five brain systems: basal ganglia (23 items), Cingular System (17 items), Temporal System (16 items), Prefrontal Cortex (24 items) and deep limbic system (20 items). Each system has a maximum score of 4, and if this punctuation is greater than 1.7 it is possible that the system is deviated from normality and implicated in AD/HD behavior. The minimal average score is 5 (Best) and the maximum is 20 (Worst). More than four is suspicious of diagnosis, six or more of a score of three or four is needed to make diagnosis. Meets the criteria for inattentiveness (six or more on questions 1-14) and also scores six or more on the cingular system questions (24-36 items), over-focused ADD subtype is suspected.

Secondary

Measure	Time frame	Description
Event-related Potentials Amplitude (ERPs)	From September to December 2012	ERPs to the GO/NOGO task will be examined for changes as a result of treatment. Assessments were made at baseline (before stimulation), after the 10-12 days of stimulation, and at 1 and 3 months after stimulation. Event related potentials (ERP) generated from a visual continuous performance task (VCPT) are employed to access the early stages of information processing (Mueller et al., 2011; Kropotov, 2008) and performing at a GO/NOGO paradigm may be used to study the mechanisms of the brain's executive functions (Falkenstein et al., 1995). Amplitude and latency of ERP activity recorded from a subject can be compared to normalized databases to predict a possible hyper or hypo function of cerebral circuits. These ERP were recorded on 19 separeted channels according international 10-20 system. Electrode names are derived by brain lobule which is is located below and position, e.g., Pz is Parietal on position zero (midline) and Cz is Central Midline.
Event-related Potentials Latency (ERPs)	From September to December 2012	ERPs to the GO/NOGO task will be examined for changes as a result of treatment. Assessments were made at baseline (before stimulation), after the 10-12 days of stimulation, and at 1 and 3 months after stimulation. Event related potentials (ERP) generated from a visual continuous performance task (VCPT) are employed to access the early stages of information processing (Mueller et al., 2011; Kropotov, 2008) and performing at a GO/NOGO paradigm may be used to study the mechanisms of the brain's executive functions (Falkenstein et al., 1995). Amplitude and latency of ERP activity recorded from a subject can be compared to normalized databases to predict a possible hyper or hypo function of cerebral circuits. These ERP were recorded on 19 separeted channels according international 10-20 system. Electrode names are derived by brain lobule which is is located below and position, e.g., Pz is Parietal on position zero (midline) and Cz is Central Midline.
Reaction Time (Behavior Task)	From September to December 2012	All subjects performed a Visual continuous performance task (VCPT) with GO/NOGO paradigm. It consists of three types of stimuli: 1) twenty animals (A), 2) twenty images of different plant (P), 3) Twenty images of people of different professions (H) which is present with an artificial sound called Novel 20msec and.Thus, each pair of stimulus is presented for 100 milliseconds, at intervals of one second of duration between each block. The objective of is to press a button as quickly as possible while observing the pairs AA, situation called GO, while trying not to press when observes other types of pairs. This latency of response (reaction time) was mensured. Pairs are called GO(AA) NOGO(AP), IGNORE(PP) and NOVEL(PH + Sound). Errors by omission (lack of response in test GO) and by commission (lack of suppression in NOGO test) were be automatically counted for each subject.
Number of Omission and Commission Errors of Behavior Task	From September to December 2012	After VCPT task, errors by Omission (lack of response in test GO) and by commission (lack of suppression in NOGO and NOVELTY test) were automatically counted for each subject.

Countries

United Kingdom

Participant flow

Recruitment details

Subjects were screened and enrolled at 3 clinics in Spain

Participants by arm

Arm	Count
Active tDCS Transcranial Direct-Current Stimulation. Patients with ADHD that receive electro-stimulation 20 sessions with 2 mAmp 1 session per day alternative days	30
Controls Healthy people that not receive tDCS	30
Total	60

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Physician Decision	2	0

Baseline characteristics

Characteristic	Controls	Active tDCS	Total
Age, Categorical <=18 years	14 Participants	19 Participants	33 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	16 Participants	11 Participants	27 Participants
Age, Continuous	33.12 years STANDARD_DEVIATION 22.8	20.06 years STANDARD_DEVIATION 13.03	25.14 years STANDARD_DEVIATION 18.09
Region of Enrollment Spain	30 participants	30 participants	60 participants
Sex: Female, Male Female	12 Participants	9 Participants	21 Participants
Sex: Female, Male Male	18 Participants	21 Participants	39 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	3 / 30	0 / 30
serious Total, serious adverse events	0 / 30	0 / 30

Outcome results

Primary

Clinical Assessment (Amen Questionnaire)

The Amen Attention Deficit Disorder (ADD) Type Questionnaire is a 71-question self-test that evaluates the ADD syndrome. 0 never, 1 rarely, 2 Occasionally, 3 Often and 4 Very Often. Consists of a series of questions that evaluate five brain systems: basal ganglia (23 items), Cingular System (17 items), Temporal System (16 items), Prefrontal Cortex (24 items) and deep limbic system (20 items). Each system has a maximum score of 4, and if this punctuation is greater than 1.7 it is possible that the system is deviated from normality and implicated in AD/HD behavior. The minimal average score is 5 (Best) and the maximum is 20 (Worst). More than four is suspicious of diagnosis, six or more of a score of three or four is needed to make diagnosis. Meets the criteria for inattentiveness (six or more on questions 1-14) and also scores six or more on the cingular system questions (24-36 items), over-focused ADD subtype is suspected.