Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With ADHD

Approximately 30 subjects aged 8-12 diagnosed with ADHD and associated feature of IA will be
recruited in this study. The PSAP is a behavioral aggression test used to evaluate behavioral
response related to impulsive aggression. The task will be combined with functional MRI to
evaluate the change in brain activity measured as BOLD signal (blood oxygenation
level-dependent) from baseline to the end of the treatment with SPN-810.

The level of neurotransmitters Glutamate and GABA will also be measured using magnetic
resonance spectroscopy (MRS).

Additionally, the improvement and severity in impulsive aggression behaviors will be assessed
using validated scales.

Inclusion Criteria:

- Otherwise healthy male or female subjects, aged 8-12 years, inclusive, at the time of
screening with primary diagnosis of ADHD and currently receiving monotherapy treatment
with an optimized US Food and Drug Administration (FDA)-approved ADHD medication.

- Impulsive aggression (IA) will be confirmed at screening using the R-MOAS and the
Vitiello Aggression Scale.

Exclusion Criteria:

- Current or lifetime diagnosis of epilepsy, major depressive disorder, bipolar
disorder, schizophrenia or related disorder, personality disorder, Tourette's
disorder, fetal alcohol syndrome, or psychosis not otherwise specified.

- Currently meeting DSM criteria for autism spectrum disorder, pervasive developmental
disorder, obsessive-compulsive disorder, post-traumatic stress disorder.

- Known or suspected IQ <70, pregnancy, substance or alcohol abuse.

- Known history of implanted brain stimulator, vagal nerve stimulator,
ventriculoperitoneal shunt, cardiac pacemaker, orthodontic braces, or implanted
medication port. Visual and hearing (≥25 dB) impairment.

- Pre-existing medical or psychological conditions that preclude being in the MRI
scanner (e.g., claustrophobia, morbid obesity, or marked anxiety about the procedure).