Clinical effectiveness of repetitive transcranial magnetic stimulation treatment in children and adolescents with neurodevelopmental disorders: A systematic review

Abstract

Neurodevelopmental disorders, including autism spectrum disorder, are common in children and adolescents, but treatment strategies remain limited. Although repetitive transcranial magnetic stimulation has been studied for neurodevelopmental disorders, there is no clear consensus on its therapeutic effects. This systematic review examined literature on repetitive transcranial magnetic stimulation for children and adolescents with neurodevelopmental disorders published up to 2018 using the PubMed database. The search identified 264 articles and 14 articles met eligibility criteria. Twelve of these studies used conventional repetitive transcranial magnetic stimulation and two studies used theta burst stimulation. No severe adverse effects were reported in these studies. In patients with autism spectrum disorder, low-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation applied to the dorsolateral prefrontal cortex may have therapeutic effects on social functioning and repetitive behaviors. In patients with attention deficit/hyperactivity disorder, low-frequency repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex and high-frequency repetitive transcranial magnetic stimulation applied to the right dorsolateral prefrontal cortex may target inattention, hyperactivity, and impulsivity. In patients with tic disorders, low-frequency repetitive transcranial magnetic stimulation applied to the bilateral supplementary motor area improved tic symptom severity. This systematic review suggests that repetitive transcranial magnetic stimulation may be a promising intervention for children and adolescents with neurodevelopmental disorders. The results warrant further large randomized controlled trials of repetitive transcranial magnetic stimulation in children with neurodevelopmental disorders.

Keywords

attention deficit/hyperactivity disorder autism spectrum disorder children and adolescents neurodevelopmental disorders repetitive transcranial magnetic stimulation

Child and adolescent neurodevelopmental disorders are common and impairing conditions with limited, brain-based treatment approaches. In 2015, the prevalence rates of autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and tic disorders in children and adolescents aged 5 to 17 years were 2.4%, 11.2%, and 0.52%, respectively (Scharf et al., 2015; U.S. Environmental Protection Agency, 2017). Timely intervention for children with neurodevelopmental disorders is critical because early disturbances in social or cognitive functioning globally impair subsequent development (Erskine et al., 2014; Sanchez-Valle et al., 2008). There are three major neurodevelopmental disorders: ASD, ADHD, and tic disorders. ASD is characterized by impairments in social interaction, communication deficits, restricted interests, and repetitive behaviors. Children with ADHD struggle with hyperactivity, impulsivity, and inattentiveness. Tic disorders, including Tourette syndrome, manifest as sudden, rapid, recurrent, and non-rhythmic motor movements and/or vocalizations (American Psychiatric Association, 2013).

Psychosocial interventions, such as applied behavior analysis or social skill training, are thought to be helpful for individuals with ASD, but the efficacies of these interventions are not well established (Virues-Ortega, Julio, & Pastor-Barriuso, 2013). Pharmacotherapy is often used to manage some symptoms (such as irritability) associated with ASD (Hirsch & Pringsheim, 2016). Common pharmacologic approaches have intolerable adverse effects, such as weight gain, insomnia, or sedation (Hirsch & Pringsheim, 2016; Storebo et al., 2015). The symptoms of ADHD, such as hyperactivity and inattention, can be treated with medications (Shang, Pan, Lin, Huang, & Gau, 2015). Stimulants, such as methylphenidate (Cortese et al., 2018), are very effective for improving ADHD symptoms in most patients. Unfortunately, 10% to 30% of ADHD patients do not benefit from these conventional therapies (Gomez et al., 2014) because patients and their families are often concerned with the associated risks and side effects (Kral, Lally, & Boan, 2017; Zhang et al., 2015). Tic disorders are often treated with antipsychotics (Weisman, Qureshi, Leckman, Scahill, & Bloch, 2013). However, the effects of medications on tic symptoms are often limited, and the side effects of antipsychotic medications are problematic in developing children. Considering the limitations of the currently available treatments for neurodevelopmental disorders, novel therapeutic and brain-based interventions with high tolerability are desperately needed for these disorders (Green & Garg, 2018).

Although the pathophysiology of neurodevelopmental disorders remains unclear, converging evidence suggests the involvement of the prefrontal cortex (PFC; Klein et al., 2017; Park et al., 2016). In particular, researchers have hypothesized that the PFC plays a major role in the pathophysiology of ASD and ADHD. Postmortem analysis has revealed enhanced neuronal density in the PFC and increased total brain weight in ASD children compared with healthy children (Courchesne et al., 2011). Furthermore, electroencephalogram (EEG) studies have indicated that children with ASD have reduced long-range connectivity in the alpha band between the frontal lobe and other brain regions. The findings could reflect a slower maturation process in children with ASD than in healthy controls (Gurau, Bosl, & Newton, 2017). A functional magnetic resonance imaging (fMRI) study indicated that less severely affected children and adolescents with ASD have higher frontal lobe activation associated with self-initiated interactions than typically developing individuals (Oberwelland et al., 2017). In addition, a voxel-based, whole-brain diffusion tensor imaging (DTI) analysis demonstrated that values of fractional anisotropy in the left dorsolateral prefrontal cortex (DLPFC) are negatively correlated with degrees of social impairment in children with ASD (Noriuchi et al., 2010). These findings suggest that structural and functional abnormalities in the PFC may underlie the clinical symptoms of ASD.

In addition, an EEG/event-related potential study using an oddball task indicated that activation in the anterior cingulate cortex and right DLPFC significantly decreases during the task in children with ADHD compared with that in healthy control subjects (Rubia, Smith, Brammer, & Taylor, 2007). An MRI study suggested that the maturation of cortical thickness lags behind approximately 3 years throughout the cerebrum in children with ADHD. Particularly, the delay in attaining peak cortical thickness is most prominent in the PFC in children with ADHD compared with healthy controls (Shaw et al., 2007). Furthermore, an fMRI study using the vigilance task demonstrated hypoactivation of the left DLPFC during the task in children with ADHD compared with healthy controls (Christakou et al., 2013). A recent meta-analysis indicated that children with ADHD have consistent functional abnormalities related to attention, as measured with fMRI, in the DLPFC, parietal cortex, and cerebellum (Hart, Radua, Nakao, Mataix-Cols, & Rubia, 2013). These findings suggest that the DLPFC plays a key role in the pathophysiology of ADHD.

The pathophysiology of tic disorders may diverge from that of ASD or ADHD. For example, the cortico-striato-thalamo-cortical circuits involving the supplementary motor area (SMA) have been implicated in the pathophysiology of Tourette syndrome (Neely, Garcia, Bankston, & Green, 2018; Peterson et al., 2001; Singer & Minzer, 2003; Stern et al., 2000). Furthermore, the SMA appears to be overactive when motor tasks are performed (Biswal et al., 1998). A recent magnetoencephalography study demonstrated that patients with chronic tic disorders have increased functional connectivity between the SMA and the motor cortex (Franzkowiak et al., 2012).

Repetitive transcranial magnetic stimulation (rTMS) is an emerging clinical treatment modality with minimal adverse effects. Conventional rTMS, such as high- and low-frequency stimulation, induces facilitatory and inhibitory modulation at the stimulated site, respectively. One of the primary advantages of rTMS is that it can stimulate specific brain areas in a non-invasive manner. To date, rTMS is primarily used as a therapeutic tool to treat depression in adults (Conelea et al., 2017; Gaynes et al., 2014; Lefaucheur et al., 2014; O’Reardon et al., 2007). Despite the increased number of clinical applications of rTMS in adult patients with neurodevelopmental disorders, a limited number of studies are available on the application of rTMS in children and adolescents with neurodevelopmental disorders (Oberman, Enticott et al., 2016). Some systematic reviews (Hameed et al., 2017; Krishnan, Santos, Peterson, & Ehinger, 2015) focused on safety aspects of rTMS application, and there is no consensus on the therapeutic effects of rTMS in children and adolescents with neurodevelopmental disorders.

Theta burst stimulation (TBS), a relatively new form of patterned rTMS, may induce therapeutic changes through neuroplasticity with lower stimulus intensities in less time than standard rTMS protocols (Huang et al., 2009), and clinical application of TBS is emerging worldwide (Suppa et al., 2016). Intermittent TBS (iTBS) induces facilitatory neuromodulation, whereas continued TBS (cTBS) induces inhibitory neuromodulation at the stimulated site. Recently, the efficacy of TBS in patients with depression has been indicated in several studies (Berlim, McGirr, Rodrigues Dos Santos, Tremblay, & Martins, 2017; Blumberger et al., 2018); however, few studies have investigated the efficacy of TBS in neurodevelopmental disorders (Abujadi, Croarkin, Bellini, Brentani, & Marcolin, 2017; Wu et al., 2014).

The present systematic review aimed to examine the therapeutic effects of rTMS and TBS in children and adolescents with neurodevelopmental disorders, such as ASD, ADHD, and tic disorders.

Methods

Search strategy

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Moher, Liberati, Tetzlaff, Altman, & PRISMA Group, 2009). A comprehensive search of articles published up to 7 February 2018 was conducted in PubMed. Terms related to transcranial magnetic stimulation (rTMS, transcranial magnetic stimulation, and repetitive transcranial magnetic stimulation) and neurodevelopmental disorders (ADHD, ASD, Asperger, attention deficit hyperactivity disorder, autism, autism spectrum disorder, childhood schizophrenia, neurodevelopmental disorders, PDD, and pervasive developmental disorder) were used in this study.

Study selection

The following inclusion criteria were applied: (1) written in English, (2) clinical studies with multiple rTMS sessions administered to patients with neurodevelopmental disorders, (3) studies including child and/or adolescent patients below 21 years of age, and (4) availability of the full-text article. The age range was extended to 21 years because individuals aged ⩽21 years are often defined as “children” (Sokhadze et al., 2012; Wang et al., 2016) or “adolescents” (Savolainen et al., 2018; Torres, Goyal, Burke-Aaronson, Gay, & Lee, 2017) according to common clinical practices in pediatrics and child psychiatry. Articles were excluded based on the following criteria: (1) animal model studies, (2) review articles, and (3) case reports.

Data extraction

Two investigators (F.M. and Y.N.) assessed the studies independently based on the eligibility criteria. The following data were extracted by F.M. and Y.N. independently from each study: study design, characteristics of participants, rTMS procedure/parameters, clinical/cognitive outcomes, medication, and adverse effects. Any discrepancies on data extraction were then reviewed, discussed, and resolved by F.M. and Y.N.

Quality assessment

There were 7 randomized controlled trials in 14 included studies. Risk of bias assessment was employed only for the randomized controlled trials using Review Manager 5.3 for the following factors: random sequence generation, allocation concealment, blinding for participants and personnel, blinding for outcome assessors, incomplete outcome data, selective reporting, and other bias (Supplemental Figure 1).

Results

The PRISMA diagram is shown in Figure 1. The PubMed search identified 264 articles, but only 14 articles met the eligibility criteria. Extracted data such as study design, stimulation protocols, and clinical effect in these studies are summarized in Tables 1 and 2. Among the 14 eligible studies, 12 used conventional rTMS (Table 1). Among the 12 studies, 8 were conducted in ASD patients (Casanova et al., 2012, 2014; Gomez et al., 2017; Panerai et al., 2014; Sokhadze et al., 2012; Sokhadze, El-Baz, Sears, Opris, & Casanova, 2014; Sokhadze, El-Baz, Tasman, et al., 2014; Wang et al., 2016); 2 were carried out in ADHD patients (Gomez et al., 2014; Weaver et al., 2012); and 2 were performed in patients with tic disorders (Bersani et al., 2013; Kwon et al., 2011). In addition, other 2 studies used TBS in patients with ASD (Abujadi et al., 2017) or chronic tic disorders (Wu et al., 2014) (Table 2).

Figure 1.

Flow diagram of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Table 1.

Conventional rTMS.

Authors (year)	Study design	Diagnosis	Comorbidity	IQ	N (neurodevelopmental disorder)	Age range (mean age), years	Type of rTMS	Site	Intensity	Frequency (Hz)	Trains	Train duration or pulses	Inter-train intervals	Total number of pulses/ session	Sessions
ASD (8)
Gómez et al. (2017)	Partial crossover trial with NIBC (rTMS and tDCS)	ASD (DSM-V, CARS, ADI-R)	–	–	Among 24 subjects, participants over 10 years and 11 months	10 to 13	LF rTMS	Left DLPFC	90% RMT	1	4	375 pulses	60 s	1500	20 (daily sessions)
Wang et al. (2016)	Clinical trial (no control)	ASD (DSM-IV-TR, ADI-R)	–	23 children IQ>80, 10 children IQ, 65–79	30	7 to 21 (12.9)	LF rTMS	Left/right DLPFC (6 left, 6 right)	90% RMT	0.5	8	–	20 s	160	12 (1 session per week)
Sokhadz et al. (2014)	Clinical trial with waitlist control	ASD (DSM-IV-TR, ADI-R)	–	IQ > 80 (WISC-IV or WASI)	42 (20 rTMS, 22 waiting list)	10 to 21 (14.7)	LF rTMS	Left/right DLPFC (6 left, 6 right, 6 left and right) in order	90% MT	1	9	20 pulses	20–30 s	180	18 (1 session per week)
Casanov et al. (2014)	Proof of feasibility study (no control)	ASD (DSM-IV-TR, ADI-R)	–	IQ > 80 (WISC-IV)	18	(13.1)	LF rTMS	left/right DLPFC (6 left, 6 right, 6 left and right)	90% RMT	0.5	8	20 pulses	20 s	160	18 (1 session per week)
Sokhadz et al. (2014)	RCT with waiting list control	ASD (DSM-IV-TR, ADI-R)	–	IQ > 80 (WISC-IV or WASI)	27	9 to 21 (14.8)	LF rTMS	Left/right DLPFC (6 left, 6 right, 6 left and right) in order	90% MT	1	9	–	20–30 s	180	18 (1 session per week)
Panerai et al. (2014)	–	Autism disorder and SID (DSM-IV-TR, CARS, PEP-R, VABS)	–	Severe to profound ID	–	–	–	–	90% RMT	–	–	–	–	–	–
Study I	Crossover trial with sham control	–	–	–	9	11.5 to 16 (13.6)	HF rTMS/LF rTMS	Left/right PrMCs	–	8/1	30	900 stimuli/30 stimuli	ー/56.4 s	900	1
Study II	RCT with sham control	–	–	–	17	(13.5)	HF rTMS/LF rTMS	Left PrMC	–	8/1	30	900 stimuli/30 stimuli	ー/56.4 s	900	10 (5 sessions per week)
Study III	Crossover trial with sham control	–	–	–	4	(16.1)	HF rTMS	Left PrMC	–	8	30	900 stimuli	–	900	5 (5 consecutive days)
Study IV	RCT (rTMS, EHI training, rTMS + EHI training)	–	–	–	13	(14.2)	HF rTMS	Left PrMC	–	8	30	900 stimuli	–	900	10 (5 sessions per week)
Sokhadz et al. (2012)	RCT with waiting list control	Autistic, Asperger (DSM-IV-TR, ADI-R)	–	90.8 ± 15.2 (WISC-IV or WASI)	40 (20 rTMS, 20 waiting list)	9 to 21 (13.5)	LF rTMS	Left/right DLPFC (6 left, 6 right) in order	90% MT	1	15	10 s	20–30 s	150	12 (1 session per week)
Casanov et al. (2012)	RCT with waiting list control	ASD (DSM-IV-TR, ADI-R)	–	Full-scale IQs > 80 (WISC-IV)	45 (25 rTMS, 20 waiting list)	9 to 19 (12.9)	LF rTMS	Left/right DLPFC (6 left, 6 right) in order	90% MT	1	15	10 s	20–30 s	150	12 (1 session per week)
ADHD (2)
Gómez et al. (2014)	Open clinical trial (no control)	ADHD	–	–	13	7 to 12	LF rTMS	Left DLPFC	90% RMT	1	–	–	1500	5 (5 consecutive days)	90% RMT
Weaver et al. (2012)	Crossover trial with sham control	ADHD (DSM-IV-TR)	Specific phobia, LD, ODD, GAD, substance abuse	–	9	14 to 21 (18.1)	HF rTMS	Right DLPFC	100% MT	10	4	26 s	2000	10 (5 sessions per week)	100% MT
Tic disorders (2)
Le et al. (2013)	Clinical trial (no control)	Tourette syndrome (DSM-IV-TR)	–	–	25	7 to 16 (10.6)	LF rTMS	SMA	110% RMT	1	20	–	1 s	1200	20 (5 sessions per week)
Kwon et al. (2011)	Clinical trial (no control)	Tourette syndrome	ADHD, major depressive disorder, OCD	IQ ⩾ 70	10	9 to 14 (9.6)	LF rTMS	SMA	100% MT	1	4	300 s	120 s	1200	10 (daily sessions)
Authors (year)	Medication			Assessment batteries/main physiological index			Main findings on closest end of the rTMS treatment (social and behavioral rating scores)				Reported effect on closest end of the rTMS treatment (others)				Adverse events
ASD (8)
Gómez et al. (2017)	–			ABC, ATEC, ADI-R, GCIS			(After NIBS) ABC, ATEC, ADI-R, decreased GCIS, improved				–				Unknown
Wang et al. (2016)	–			ABC, RBS-R, HRV (R-R interval, pNN50, NN50, SD R-R interval, LF, HF, LF/HF ratio), SCL			ABC, decreased stereotypy, hyperactivity, and inappropriate speech scores, RBS-R, decreased stereotype behavior, ritualistic/sameness and total scores				HRV, (linear) increased R-R interval, pNN50, NN50, SD R-R interval, HF (linear) decreased, LF, LF/HF ratio SCL, (linear) decreased				Unknown
Sokhadze et al. (2014)	–			RBS-R, ABC, behavioral responses of Kanizsa test (RT, accuracy)			ABC, decreased lethargy and hyperactivity, RBS-R, decreased stereotype behavior, compulsive behavior, ritualistic/sameness behavior and total scores				Behavioral responses of Kanizsa test, decreased total error percentage, normative post-error RT,				Unknown
Casanova et al. (2014)	–			ABC, RBS-R, HRV (R-R interval, SDNN, RMSSD, pNN50, LF, HF, LF/HF ratio), SCL			ABC, decreased irritability, lethargy, and hyperactivity scores, RBS-R, decreased stereotyped behavior, ritualistic/sameness behavior and total scores				HRV, increased R-R interval, SDNN, and HF decreased LF/HF ratio SCL, decreased				Unknown
Sokhadze et al. (2014)	–			ABC, RBS-R, behavioral response of Kanizsa test (RT, accuracy, post-error RT)			ABC, decreased irritability, lethargy, and hyperactivity scores, RBS-R, decreased stereotype behavior, ritualistic behavior and total scores				Behavioral response of Kanizsa test, post-error RT slowing and higher accuracy of responses				Unknown
Panerai et al. (2014)	–			PEP-R, psychoeducational profile—revised; eye–hand coordination			–				–				–
Study I	–			–			–				PEP-R, improved				Unknown
Study II	–			–			–				PEP-R, improved				Unknown
Study III	–			–			–				PEP-R, improved				Unknown
Study IV	–			–			–				PEP-R, improved (TMS + EHI training improved compared to others)				Unknown
Sokhadze et al. (2012)	–			Behavioral responses of Kanizsa test (RT, post-error RT change, commission errors, omission errors)			ー				Behavioral responses of Kanizsa test, decreased omission errors, slower Post-error RT				Unknown
Casanova et al. (2012)	–			ABC (irritability and hyperactivity), SRS (social awareness), RBS-R, behavioral responses of Kanizsa test (RT, accuracy)			ABC, decreased irritability scores SRS, no significant change, RBS-R, decreased				Behavioral responses of Kanizsa test, decreased response errors				Unknown
Authors (year)	Medication			Assessment batteries/main physiological index			Main findings on closest end of the rTMS treatment (social and behavioral rating scores)				Reported effect on closest end of the rTMS treatment (others)				Adverse events
ADHD (2)
Gómez et al. (2014)	Authors asked not to change in medication until the end of the study			SCL (symptoms checklist) for ADHD			SCL for ADHD, significant improvement; specifically, inattentiveness symptoms at school (initial score, 16.7 vs final, 8.6) and the hyperactivity/impulsivity at home (initial score, 30.8 vs final, 11.4)				–				A slight headache or local discomfort (70%), neck pain (20%)
Weaver et al. (2012)	Wash out for a period of 7 to 12 days before the initial neuropsychological testing and during the remainder of the study			CGI, ADHD-IV scale, neuropsychological domain (working memory, impulsivity, sustained attention, long-term memory, flexibility, motor)			CGI, ADHD-IV scale, improved across the study phase (no difference between active and sham)				Neuropsychological domain, no significant difference				Mild headaches and scalp discomfort (n = 3)
Tic disorders (2)
Le et al. (2013)	Remained on their usual medications and doses had been stable for at least 12 weeks (tiapride, topiramate, haloperidol, inosine, trihexyphenidyl, or traditional Chinese medicine Jingling liquid). Medications, such as some neuroleptics (including chlorpromazine) that might lower the seizure threshold were ceased			YGTSS, CGI, SNAP-IV, SCAS, Kovacs’ CSI, attention test (error rate),			YGTSS, CGI, Kovacs’ CSI, improved SNAP-IV, SCAS, no significant change				Attention test (error rate), decreased				None
Kwon et al. (2011)	TS medications (remain for 3 months prior to starting study and throughout the study)			YGTSS, CGI-TS, the Korean version of Conners’ ADHD scale, the Korean version of the DuPaul ADHD scale, the Children’s Depression Inventory, the Spielberger State/Trait Anxiety scale			YGTSS, CGI-TS, improved the Korean version of Conners’ ADHD scale, the Korean version of the DuPaul ADHD scale, the Children’s Depression Inventory, the Spielberger State/Trait Anxiety scale, no significant change				–				None

ABC: aberrant behavior checklist; ADHD: attention deficit/hyperactivity disorder; ASD: autism spectrum disorder; ATEC: autism treatment evaluation checklist; CGI: clinical global impressions; CY-BOCS: children’s Yale–Brown obsessive-compulsive scale; DLPFC: dorsolateral prefrontal cortex; DTI: diffusion tensor imaging; GAD: generalized anxiety disorder; GCIS: global clinical impression scale; GTS-QOL: Gilles de la Tourette syndrome–quality of life scale; LD: learning disability; ID: intellectual disability; OCD: obsessive compulsive disorder; ODD: oppositional defiant disorder; PEP-R: psychoeducational profile—revised; PFC: prefrontal cortex; PrMC: premotor cortex; RBS-R: repetitive behavior scale—revised; RCT: randomized controlled trial; RMT: resting motor threshold; RT: reaction time; rTMS: repetitive transcranial magnetic stimulation; SCL: symptoms checklist; SMA: supplemental motor area; SRS: social responsiveness scale; TMS: transcranial magnetic stimulation; TS: Tourette syndrome; WCST: Wisconsin card sorting test; YGTSS: Yale global tic severity scale total tic score.

Table 2.

Theta burst stimulation (TBS).

Authors (year)	Study design	Diagnosis	Comorbidity	IQ	N (neurodevelopmental disorder)	Age range (mean age), years	Type of rTMS	Site	Intensity	Frequency (Hz)	Trains	Train duration or pulses	Inter-train intervals	Total number of pulses/ session	Sessions
ASD (1)
Abujadi et al. (2017)	Open clinical trial (no control)	ASD	–	IQs > 50 (WISC-III)	10	9 to 17	iTBS	right DLPFC	100% MT	50	30	8 s	2 s	–	15 (5 days per week)
Tic disorders (1)
Wu et al. (2014)	RCT with sham control	Chronic tic disorder (DSM-IV-TR)	ADHD, OCD	–	12 (6 rTMS, 6 sham)	13.5	cTBS	SMA	90% RMT	30	4	600 pulses	The first and second cTBS trains were delivered 15 min apart. The third and fourth cTBS trains were delivered 60 and 75 min after the first cTBS	2400	2 (2 consecutive days)
Authors (year)	Medication			Assessment batteries/physiological index			Main findings on closest end of the rTMS treatment (social and behavioral rating scores)				Reported effect on closest end of the rTMS treatment (others)			Adverse events
ASD (1)
Gómez et al. (2017)	–			RBS-R, Y-BOCS, WCST, Stroop test			RBS-R, improved Y-BOCS, improved mean overall compulsion subscale scores				WCST, improved perseverative errors Stroop test, improved time for completion			None
Tic disorders (1)
Wu et al. (2014)	No medication changes within 10 days of receiving cTBS (topiramate, methylphenidate, sertraline, clonazepam, guanfacine, risperidone, guanfacine, aripiprazole, atomoxetine, baclofen, gabapentin, venlafaxine, clonidine, dextroamphetamine, haloperidol)			YGTSS, GTS-QOL, RVTRS, PUTS, CY-BOCS, DuPaul ADHD rating scale scores, fMRI activation during finger tapping			YGTSS, GTS-QOL, RVTRS, PUTS, CY-BOCS, DuPaul ADHD rating scale scores, no significant difference comparing active and sham				fMRI activation during finger tapping, significantly decreased over SMA, left M1 and right M1			Three participants complained of mild adverse events (abdominal pain, headaches, dry eyes)

ABC: aberrant behavior checklist; ADHD: attention deficit/hyperactivity disorder; ASD: autism spectrum disorder; cTBS: continuous theta burst stimulation; CY-BOCS: children’s Yale–Brown obsessive-compulsive scale; DLPFC: dorsolateral prefrontal cortex; GTS-QOL: Gilles de la Tourette syndrome–quality of life scale; iTBS: intermittent theta burst stimulation; PUTS: premonitory urge for tics scale; RBS-R: repetitive behavior scale—revised; RCT: randomized controlled trial; RMT: resting motor threshold; RT: reaction time; rTMS: repetitive TMS; RVTRS: rush videotaped tic rating scale; SCL: symptoms checklist; SMA: supplemental motor area; TBS: theta burst stimulation; TMS: transcranial magnetic stimulation; TS: Tourette syndrome; WCST: Wisconsin card sorting test; YGTSS: Yale global tic severity scale total tic score.

Conventional rTMS for neurodevelopmental disorders

Findings of rTMS for ASD

A total of four different types of rTMS intervention methods were identified in the eight studies. Findings are organized according to the rTMS treatment protocols.

In three studies, low-frequency rTMS, which was applied to the left, right, and bilateral DLPFC in separate sessions (six sessions for each stimulation site), had positive effects on social and behavioral rating scores, as indexed with the aberrant behavior checklist (ABC) or repetitive behavior scale—revised (RBS-R) (Casanova et al., 2014; Sokhadze, El-Baz, Sears, et al., 2014; Sokhadze, El-Baz, Tasman, et al., 2014). Symptoms such as irritability, hyperactivity, and lethargy (social withdrawal) on the ABC rating scale improved in all studies (Casanova et al., 2014; Sokhadze, El-Baz, Sears, et al., 2014; Sokhadze, El-Baz, Tasman, et al., 2014). Among the three studies, two showed improved behavioral responses in the visual task of Kanizsa illusion figures, indicating the decreased response errors and normalized post-error reaction time (Sokhadze, El-Baz, Sears, et al., 2014; Sokhadze, El-Baz, Tasman, et al., 2014).

Low-frequency rTMS was applied to the left and right DLPFC in separate sessions (six sessions for each stimulation site) in other three studies (Casanova et al., 2012; Sokhadze et al., 2012; Wang et al., 2016). Among the three studies, two showed positive effects on social and behavioral rating scores, as measured with the ABC (irritability, stereotypy, hyperactivity, and inappropriate speech scores) and RBS-R (stereotype behavior, ritualistic/sameness, and total scores) (Casanova et al., 2012; Wang et al., 2016). In addition, the behavioral and error responses in the visual task of Kanizsa illusion figures improved in two of the three studies (Casanova et al., 2012; Sokhadze et al., 2012). Furthermore, one study showed the normalized post-error reaction time (Sokhadze et al., 2012).

In one study, low-frequency rTMS, which was used to the left DLPFC, improved social and behavioral rating scores, as measured with the ABC and autism treatment evaluation checklist (Gomez et al., 2017). However, the RBS-R or behavioral responses were not investigated in this study.

In another study, high-frequency rTMS, which was applied to the left premotor cortex in ASD patients with severe intellectual disability, improved eye–hand coordination, as assessed with the psychoeducational profile—revised (Panerai et al., 2014). Notably, these studies did not find adverse events caused by rTMS for ASD. There was no description of concurrent medications during rTMS treatment in the eight studies focusing on ASD.

Findings of rTMS for ADHD

In total, two rTMS clinical trials were performed in children and adolescents with ADHD (Gomez et al., 2014; Weaver et al., 2012). Although the evaluation methods were different in the two studies, the behavioral rating scores improved compared with the baseline in both studies. In particular, in one study without controls, 1-Hz stimulation on the left DLPFC for five sessions improved the scores of the symptoms checklist (SCL) in patients with ADHD, especially in those with inattentiveness at school and hyperactivity/impulsivity at home (Gomez et al., 2014). Weaver et al. (2012) applied 10 sessions of 10-Hz rTMS over the right DLPFC as an active rTMS phase in a crossover design. Scores on the clinical global impressions (CGI) and ADHD-IV scale significantly decreased compared with the baseline, although no differences were observed between active and sham groups (Weaver et al., 2012). Notably, both studies found some mild adverse events (such as slight headache, local discomfort, or neck pain) associated with rTMS. With regard to medications, concomitant medications were fixed during one study (Gomez et al., 2014); however, medications were washed out for 7 to 12 days before another study, and the medication-free condition was maintained during the study (Weaver et al., 2012).

Findings of rTMS for tic disorders

To date, rTMS was applied in patients with tic disorders in two clinical trials (Bersani et al., 2013; Kwon et al., 2011). Scores on both the Yale global tic severity scale (YGTSS) and the CGI improved in these two studies. Particularly, 1-Hz rTMS was applied to the SMA with 1200 pulses per session for 20 sessions in one study (Bersani et al., 2013), and the same rTMS protocol with 10 sessions was used in another study (Kwon et al., 2011). In both studies, medications were maintained for at least 12 weeks prior to rTMS and at a steady dose throughout rTMS. In addition, the rating scales related to other symptoms, such as attention deficit or anxiety, did not change after rTMS treatment (Kwon et al., 2011). No adverse effects were observed in these studies.

TBS for children and adolescents with neurodevelopmental disorders

TBS was used in patients with ASD and chronic tic disorders in the remaining 2 studies among the 14 selected studies (Abujadi et al., 2017; Wu et al., 2014) (Table 2).

Findings of TBS for ASD

Abujadi et al. (2017) applied iTBS for children and adolescents with ASD, and scores of both RBS-R and Yale–Brown obsessive-compulsive scale improved after 15 sessions of iTBS over the right DLPFC. The executive function including perseverative errors and time for completion, which were respectively assessed with the Wisconsin card sorting test and Stroop test, improved in this study. Notably, no adverse effects were observed in this study. Medication information during the TBS treatment was not described in this study.

Findings of TBS for tic disorders

Wu et al. (2014) used cTBS with two sessions for two consecutive days over the SMA for children and adolescents with chronic tic disorders, and they assessed the clinical effects using rating scales such as the YGTSS and Gilles de la Tourette syndrome–quality of life. No significant differences were found between active and sham TBS groups. In total, three participants complained of mild adverse events: abdominal pain, headaches, and dry eyes. However, there was no description of the causality of adverse events during cTBS treatment in this study. Medications were administered mostly in 10 days before the cTBS treatment and maintained during the treatment.

Discussion

This systematic review demonstrates the potential clinical effects of rTMS in some children and adolescents with neurodevelopmental disorders. In patients with ASD, low-frequency rTMS applied to the left DLPFC or iTBS applied to the right DLPFC had beneficial effects on stereotypy, hyperactivity, inappropriate speech scores, irritability, and lethargy. In patients with ADHD, low-frequency rTMS applied to the left DLPFC improved hyperactivity, impulsivity, and inattentiveness. In patients with tic disorders, low-frequency rTMS applied to the SMA ameliorated tic symptoms. A few mild adverse effects were identified in the present systematic review.

The optimal rTMS protocol for ASD or ADHD may be different from that for depression despite the same stimulation site, the DLPFC. In general, high-frequency rTMS is applied to the left DLPFC in most studies (Conelea et al., 2017; Gaynes et al., 2014) based on the assumption that neuroplasticity declines in the DLPFC in patients with depression (Crabtree et al., 2017; Noda et al., 2018; Zheng & Zhang, 2015). In contrast, neuroplasticity is hypothesized to increase in patients with neurodevelopmental disorders, particularly in those with ASD (Oberman, Ifert-Miller et al., 2016; Oberman & Pascual-Leone, 2014). Thus, the differences in presumed pathophysiology account for differences in rTMS protocols used in neurodevelopmental and depressive disorders. In addition, low-frequency rTMS induces inhibitory neuromodulation, while high-frequency rTMS induces facilitatory neuromodulation at the stimulated site (Funke & Benali, 2011; Lozeron et al., 2016). It has been recently demonstrated that ASD patients have decreased cortical inhibition (Banerjee et al., 2013; Enticott, Rinehart, Tonge, Bradshaw, & Fitzgerald, 2010; Vattikuti & Chow, 2010), which could result in cortical excitation/inhibition (E/I) imbalance. Therefore, we speculate that low-frequency rTMS may increase inhibitory function at the stimulated site, leading to improved symptoms in children and adolescents with ASD.

Therapeutic effects of rTMS and TBS in ASD

This study found that low-frequency rTMS to the left DLPFC and iTBS to the right DLPFC had positive effects on behaviors in children and adolescents with ASD. These different therapeutic interventions have been thought to cause similar effects through transcallosal inhibition, and they improve symptoms (such as irritability, hyperactivity, repetitive behaviors, and lethargy) that tend to be resistant to pharmacotherapy (Hirsch & Pringsheim, 2016). As mentioned in the introduction, children and adolescents with ASD are assumed to have increased numbers of cortical columns and neurons in the PFC (Ameis & Catani, 2015), resulting in greater total brain weight in ASD children than in healthy controls (Courchesne et al., 2011). Furthermore, the neuroanatomical alterations may induce inappropriate overactivation in the PFC, thus leading to dysfunctional connectivity in the PFC in children and adolescents with ASD. Indeed, Uddin and colleagues proposed that over-connectivity in the default mode network involving the PFC is more prevalent in children and adolescents with ASD (Uddin, Supekar, Lynch et al., 2013; Uddin, Supekar, & Menon, 2013). Therefore, suppressive effects of low-frequency rTMS on the DLPFC could normalize functional connectivity in the PFC in children and adolescents with ASD. Interestingly, the positive effects of conventional rTMS on repetitive behaviors were noted in children and adolescents with ASD in the included studies. Repetitive behaviors are hypothesized to be related to the pathophysiology of the reward system involving the striatum (Kohls, Yerys, & Schultz, 2014; Langen et al., 2014). Kohls et al. (2014) proposed that overvaluation of the reward system may contribute to excessive routine behaviors, which cause resistance to changes. Accumulating evidence suggests that the striatum is functionally connected to the DLPFC (Avissar et al., 2017; Biswal et al., 1998; Haber & Knutson, 2010; Jarbo & Verstynen, 2015). Strafella and colleagues demonstrated that high-frequency rTMS administered to the DLPFC could increase the release of endogenous dopamine from the caudate nucleus (Strafella, Paus, Barrett, & Dagher, 2001; Strafella, Paus, Fraraccio, & Dagher, 2003). Conversely, suppressive effects of low-frequency rTMS on the DLPFC could induce dopaminergic neuromodulation in patients with ASD, thus alleviating symptoms such as repetitive behaviors.

Previous studies suggest that the effect of the pharmacological intervention on lethargy is limited, although pharmacotherapy may improve other symptoms of ASD, including irritability, hyperactivity, and repetitive behaviors (Hirsch & Pringsheim, 2016). However, rTMS can improve irritability, hyperactivity, repetitive behaviors, and lethargy (Casanova et al., 2014; Sokhadze, El-Baz, Sears, et al., 2014; Sokhadze, El-Baz, Tasman, et al., 2014). All currently available antipsychotics, including risperidone and aripiprazole, block postsynaptic D2 receptors and inhibit excessive transmission of dopamine in the mesolimbic system, thus alleviating the psychotic symptoms (Miyamoto, Duncan, Marx, & Lieberman, 2005) and improving repetitive behaviors in ASD (McDougle et al., 1998). In addition, low-frequency rTMS over the left DLPFC may stabilize the dopamine release at the stimulated site (Strafella et al., 2001, 2003), possibly leading to beneficial effects on lethargy in ASD (Casanova et al., 2014; Sokhadze, El-Baz, Sears, et al., 2014; Sokhadze, El-Baz, Tasman, et al., 2014). Therefore, unlike antipsychotics, rTMS may exert the therapeutic effect on social lethargy by modulating other neurotransmitter-related systems such as GABAergic and glutamatergic functions (Baeken, Lefaucheur, & Van Schuerbeek, 2017; Dlabac-de Lange et al., 2017; Dubin et al., 2016). However, based on the findings in previous studies, the impact of DLPFC rTMS on social impairment in ASD remains elusive. For example, three studies indicate the positive effect of rTMS on lethargy (Casanova et al., 2014; Sokhadze, El-Baz, Sears, et al., 2014; Sokhadze, El-Baz, Tasman, et al., 2014), whereas two studies suggest the negative impact of DLPFC rTMS on lethargy (Wang et al., 2016) or social awareness (Sokhadze et al., 2010). Therefore, it is premature to conclude that rTMS has positive effects on lethargy.

Therapeutic effects of rTMS and TBS in ADHD

This systematic review found that low-frequency rTMS to the left DLPFC and high-frequency rTMS to the right DLPFC improved symptoms, such as inattentiveness, in children and adolescents with ADHD. The study by Gomez et al. had no control subjects, and the study by Weaver et al. did not find significant differences between patients and sham controls; therefore, it is difficult to conclude whether rTMS has beneficial effects on ADHD based solely on the findings in these two studies. Moreover, these two studies have some limitations, including small sample sizes and short-term study durations. Therefore, more rigorous studies are warranted. However, Gomez et al. demonstrated that scores on the SCL decreased by half in patients with ADHD following rTMS treatment. Given the findings in previous studies that used placebo controls (Goodman et al., 2017; Philipsen et al., 2015), there might be some therapeutic effects of rTMS beyond placebo effects. In addition, only subjects with active rTMS showed improved symptoms during the second phase of study after crossover.

Findings in imaging studies seem to warrant further studies on rTMS application in ADHD. Using fMRI, Rubia et al. (2007) found decreased activation of the right DLPFC during an oddball task. Moreover, using fMRI, Chrstakou et al. (2013) found decreased activation of the left DLPFC during a vigilance task in ADHD children compared with healthy controls. Children with ADHD showed improved inattentiveness and hyperactivity/impulsivity in one study in this review (Gomez et al., 2014). Although hyperactivity or impulsivity declines with age, inattentiveness is suggested to be persistent over a lifetime (Biederman, Mick, & Faraone, 2000; Larsson, Lichtenstein, & Larsson, 2006). Therefore, effective treatments for inattention throughout the life cycle are needed. Compared with healthy controls, children with ADHD show dysfunction in the left DLPFC during the sustained attention task (Christakou et al., 2013). Because the DLPFC is considered to be involved in the top-down attentional control (Silton et al., 2010), persistent dysfunction of the DLPFC may account for the pathophysiology of ADHD (Hart et al., 2013). Regarding TBS treatment, He et al. (2013) found that iTBS to the right DLPFC induced a significant improvement in the alerting and executive control efficiency on the attention network test in healthy young adults, suggesting the beneficial effects of iTBS on attentional ability. Taken together, these findings support the speculation that stimulation of the DLPFC may improve inattention in children and adolescents with ADHD. Notably, these two forms of rTMS, low-frequency rTMS and iTBS, induce opposite effects at the same stimulation site. However, because there is a transcallosal inhibition between the left and the right DLPFC through the corpus callosum (Fleming & Newham, 2017), low-frequency rTMS to the left DLPFC could induce facilitatory effects on the contralateral stimulation site (i.e. the right DLPFC), while iTBS to the right DLPFC could induce inhibitory effects on the contralateral stimulation site (i.e. the left DLPFC). Therefore, from a neurophysiological point of view, low-frequency rTMS to the left DLPFC and iTBS to the right DLPFC may confer similar effects.

Moreover, previous DTI studies have consistently demonstrated that white matter anomalies are present in the corpus callosum in children with ADHD (Aoki, Cortese, & Castellanos, 2018; Gilliam et al., 2011). Recently, Kaller et al. found that stronger connectivity between the left and the right DLPFC through the corpus callosum was associated with poorer planning performance in post-adolescents (Kaller et al., 2015). Thus, rTMS to the DLPFC might attenuate impulsivity in children with ADHD through improving their planning ability, in which the DLPFC is involved.

Therapeutic effects of rTMS and TBS in tic disorders

Two studies showed that low-frequency rTMS to the SMA improved tic symptoms in children with Tourette syndrome (Bersani et al., 2013; Kwon et al., 2011).

However, because both are open-label studies, more rigorous studies are needed to confirm these findings. Hyperactivation of the SMA or increased functional connectivity between the SMA and the motor cortex (Biswal et al., 1998; Franzkowiak et al., 2012) could be suppressed by low-frequency rTMS. Furthermore, dopaminergic disturbances in the subcortical basal ganglia are considered to be involved in tic disorders (Godar, Mosher, Di Giovanni, & Bortolato, 2014; Maia & Conceicao, 2017). Thus, rTMS may modulate the dopaminergic system involved in the reward system (Stanford et al., 2013).

The findings are inconsistent with those obtained in previous rTMS studies in adults with tic disorders, which suggest that rTMS has no beneficial effects (Landeros-Weisenberger et al., 2015; Münchau et al., 2002; Orth et al., 2005). Liu et al. (2013) found that a longer duration of tic symptoms was related to abnormalities in the anterior thalamic radiations. Therefore, the inhibitory pathways in the circuits could be differently impaired in different ages of patients, and the speculation may account for the differences in the effects of rTMS between children and adults.

In addition, inhibitory cTBS to the SMA had no significant impact in this population (Wu et al., 2014). However, because this study applied only two cTBS sessions in six subjects diagnosed with different tic disorders (Landeros-Weisenberger et al., 2015), it is difficult to conclude that cTBS is not effective in this population. Thus, further studies are needed to examine the clinical effects of cTBS over the SMA in patients with tic disorders.

Limitations

This study has several limitations. First, we searched articles only in PubMed because it was the only available search engine in our institution. Second, this systematic review focused on the clinical effectiveness of rTMS, indexed mainly with social and behavioral rating scores, in children and adolescents with neurodevelopmental disorders. Thus, biological measures, such as physiological indexes, were not investigated in this review. Third, this study reviewed the clinical effectiveness of rTMS only in children and adolescents with neurodevelopmental disorders, and the studies on neurodevelopmental disorders in adults were not included in this review. Notably, one randomized controlled trial showed a significant improvement in social function–related symptoms in adults with ASD following active rTMS (Enticott et al., 2014). However, the effectiveness of rTMS treatment in adults with neurodevelopmental disorders is controversy. Therefore, further studies are needed to summarize rTMS studies on neurodevelopmental disorders in adults. Fourth, we focused on clinical studies that consisted of multiple sessions of rTMS in patients with neurodevelopmental disorders, and clinical and/or cognitive effects induced by a single session of rTMS were not covered in this study. Fifth, most included rTMS studies targeted at the PFC in patients with neurodevelopmental disorders. Therefore, further studies are needed to investigate pathophysiological bases at the cortical areas other than the PFC and examine the clinical effectiveness of rTMS to the other cortical areas in patients with these disorders. Sixth, the sample sizes in these included studies were small. The small number of patients in each study might prevent meaningful conclusions from being drawn about the impacts of disease severity, adjunctive medications and interventions, and treatment duration on rTMS outcomes. Because adequate controls and blinding for outcome assessors and participants were lacking in the included studies, the findings in this systematic review should be considered preliminary and interpreted with caution. Therefore, more rigorous assessments are warranted to determine the potential efficacy. Seventh, mixed pediatric and adolescent patients were included in some studies, despite potential differences in brain development and function between the two groups of patients. Eighth, some studies did not assess clinical scores. Even if ratings were conducted, a few studies did not report subscale scores in detail.

Future directions

Early intervention with rTMS for children and adolescents with treatment-resistant neurodevelopmental disorders could improve some key symptoms of these disorders. Therefore, further well-designed studies addressing current limitations and knowledge gaps are warranted.

To date, most of the previous rTMS studies focused on only one particular disorder (ASD, ADHD, or tic disorders). However, there are significant similarities in the symptoms among these disorders. Such similarities might indicate common underlying pathophysiology among these disorders. Therefore, it may be helpful to assess the neurobiological mechanisms of these neurodevelopmental disorders with transdiagnostic approaches, comprehensive clinical and cognitive batteries (Funabiki, Kawagishi, Uwatoko, Yoshimura, & Murai, 2011), and reliable biological measures. Therefore, further studies are needed to determine the neural bases of specific symptom clusters, and the findings could allow scientists to target specific symptoms with rTMS intervention and pave the way for personalized medicine in the future.

In addition, TBS was only used in two included studies. However, considering the improved time burden for patients and families, TBS seems to be worth further investigation as a promising treatment option. TBS has less inconvenience and greater feasibility especially in children and adolescents who have daily activities. In addition, TBS possibly benefits children with hyperactivity characteristics because they often have difficulty sitting in the same place for a long time.

Conclusion

This systematic review indicates beneficial effects of rTMS in children and adolescents with neurodevelopmental disorders. The present findings suggest that rTMS may ameliorate ASD symptoms (such as lethargy) that conventional treatments have failed to address to date. The results warrant further rTMS studies with larger sample sizes and systematic clinical assessments (including neurophysiological markers) in patients with neurodevelopmental disorders.

Supplemental Material

AUT822502_Lay_Abstract – Supplemental material for Clinical effectiveness of repetitive transcranial magnetic stimulation treatment in children and adolescents with neurodevelopmental disorders: A systematic review

Supplemental material, AUT822502_Lay_Abstract for Clinical effectiveness of repetitive transcranial magnetic stimulation treatment in children and adolescents with neurodevelopmental disorders: A systematic review by Fumi Masuda, Shinichiro Nakajima, Takahiro Miyazaki, Ryosuke Tarumi, Kamiyu Ogyu, Masataka Wada, Sakiko Tsugawa, Paul E Croarkin, Masaru Mimura and Yoshihiro Noda in Autism

Supplemental Material

AUT822502_Supplemental_material – Supplemental material for Clinical effectiveness of repetitive transcranial magnetic stimulation treatment in children and adolescents with neurodevelopmental disorders: A systematic review

Supplemental material, AUT822502_Supplemental_material for Clinical effectiveness of repetitive transcranial magnetic stimulation treatment in children and adolescents with neurodevelopmental disorders: A systematic review by Fumi Masuda, Shinichiro Nakajima, Takahiro Miyazaki, Ryosuke Tarumi, Kamiyu Ogyu, Masataka Wada, Sakiko Tsugawa, Paul E Croarkin, Masaru Mimura and Yoshihiro Noda in Autism

Footnotes

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Supplemental material

Supplemental material for this article is available online.

ORCID iD

Yoshihiro Noda

References

Abujadi

Croarkin

P. E.

Bellini

B. B.

Brentani

Marcolin

M. A.

(2017). Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: An open-label pilot study. Revista brasileira de psiquiatria, 40, 309–311. doi:10.1590/1516-4446-2017-2279

Ameis

S. H.

Catani

(2015). Altered white matter connectivity as a neural substrate for social impairment in autism spectrum disorder. Cortex, 62, 158–181. doi:10.1016/j.cortex.2014.10.014

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author.

Aoki

Cortese

Castellanos

F. X.

(2018). Research review: Diffusion tensor imaging studies of attention-deficit/hyperactivity disorder: Meta-analyses and reflections on head motion. Journal of Child Psychology and Psychiatry and Allied Disciplines, 59, 193–202. doi:10.1111/jcpp.12778

Avissar

Powell

Ilieva

Respino

Gunning

F. M.

Liston

Dubin

M. J.

(2017). Functional connectivity of the left DLPFC to striatum predicts treatment response of depression to TMS. Brain Stimulation, 10, 919–925. doi:10.1016/j.brs.2017.07.002

Baeken

Lefaucheur

J. P.

Van Schuerbeek

(2017). The impact of accelerated high frequency rTMS on brain neurochemicals in treatment-resistant depression: Insights from (1)H MR spectroscopy. Clinical Neurophysiology, 128, 1664–1672. doi:10.1016/j.clinph.2017.06.243

Banerjee

Garcia-Oscos

Roychowdhury

Galindo

L. C.

Hall

Kilgard

M. P.

Atzori

(2013). Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism. The International Journal of Neuropsychopharmacology, 16, 1309–1318. doi:10.1017/S1461145712001216

Berlim

M. T.

McGirr

Rodrigues Dos Santos

Tremblay

Martins

(2017). Efficacy of theta burst stimulation (TBS) for major depression: An exploratory meta-analysis of randomized and sham-controlled trials. Journal of Psychiatric Research, 90, 102–109. doi:10.1016/j.jpsychires.2017.02.015

Bersani

F. S.

Minichino

Enticott

P. G.

Mazzarini

Khan

Antonacci

. . . Biondi

(2013). Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: A comprehensive review. European Psychiatry, 28(1), 30–39. doi:10.1016/j.eurpsy.2012.02.006

10.

Biederman

Mick

Faraone

(2000). Age-dependent decline of symptoms of attention deficit hyperactivity disorder: Impact of remission definition and symptom type. The American Journal of Psychiatry, 157, 816–818.

11.

Biswal

Ulmer

J. L.

Krippendorf

R. L.

Harsch

H. H.

Daniels

D. L.

Hyde

J. S.

Haughton

V. M.

(1998). abnormal cerebral activation associated with a motor task in Tourette syndrome. American Journal of Neuroradiology, 19, 1509–1512.

12.

Blumberger

D. M.

Vila-Rodriguez

Thorpe

K. E.

Feffer

Noda

Giacobbe

. . . Downar

(2018). Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): A randomised non-inferiority trial. The Lancet, 391, 1683–1692. doi:10.1016/s0140-6736(18)30295-2

13.

Casanova

M. F.

Baruth

J. M.

El-Baz

Tasman

Sears

Sokhadze

(2012). Repetitive transcranial magnetic stimulation (rTMS) modulates event-related potential (ERP) indices of attention in autism. Translational Neuroscience, 3, 170–180.

14.

Casanova

M. F.

Hensley

M. K.

Sokhadze

E. M.

El-Baz

A. S.

Wang

Sears

(2014). Effects of weekly low-frequency rTMS on autonomic measures in children with autism spectrum disorder. Frontiers in Human Neuroscience, 8, Article 851. doi:10.3389/fnhum.2014.00851

15.

Christakou

Murphy

C. M.

Chantiluke

Cubillo

A. I.

. . . Rubia

(2013). Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with autism. Molecular Psychiatry, 18, 236–244. doi:10.1038/mp.2011.185

16.

Conelea

C. A.

Philip

N. S.

Yip

A. G.

Barnes

J. L.

Niedzwiecki

M. J.

Greenberg

B. D.

. . . Carpenter

L. L.

(2017). Transcranial magnetic stimulation for treatment-resistant depression: Naturalistic treatment outcomes for younger versus older patients. Journal of Affective Disorders, 217, 42–47. doi:10.1016/j.jad.2017.03.063

17.

Cortese

Adamo

Del Giovane

Mohr-Jensen

Hayes

Carucci

. . . Cipriani

(2018). Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: A systematic review and network meta-analysis. The Lancet Psychiatry, 5, 727–738.

18.

Courchesne

Mouton

Calhoun

Semendeferi

Ahrens-Barbeau

Hallet

. . . Pierce

(2011). Neuron number and size in prefrontal cortex of children with autism. Journal of the American Medical Association, 306, 2001–2010.

19.

Crabtree

G. W.

Sun

Kvajo

Broek

J. A.

Fenelon

McKellar

. . . Gogos

J. A.

(2017). Alteration of neuronal excitability and short-term synaptic plasticity in the prefrontal cortex of a mouse model of mental illness. Journal of Neuroscience, 37, 4158–4180. doi:10.1523/JNEUROSCI.4345-15.2017

20.

Dlabac-de Lange

J. J.

Liemburg

E. J.

Bais

van de Poel-Mustafayeva

A. T.

de Lange-de Klerk

E. S. M.

Knegtering

Aleman

. (2017). Effect of bilateral prefrontal rTMS on left prefrontal NAA and Glx levels in schizophrenia patients with predominant negative symptoms: An exploratory study. Brain Stimulation, 10, 59–64. doi:10.1016/j.brs.2016.08.002

21.

Dubin

M. J.

Mao

Banerjee

Goodman

Lapidus

K. A. B.

Kang

. . . Shungu

D. C.

(2016). Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy. Journal of Psychiatry & Neuroscience, 41(2), E37–E45. doi:10.1503/jpn.150223

22.

Enticott

P. G.

Fitzgibbon

B. M.

Kennedy

H. A.

Arnold

S. L.

Elliot

Peachey

. . . Fitzgerald

P. B.

(2014). A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. Brain Stimulation, 7, 206–211. doi:10.1016/j.brs.2013.10.004

23.

Enticott

P. G.

Rinehart

N. J.

Tonge

B. J.

Bradshaw

J. L.

Fitzgerald

P. B.

(2010). A preliminary transcranial magnetic stimulation study of cortical inhibition and excitability in high-functioning autism and Asperger disorder. Developmental Medicine and Child Neurology, 52(8), e179–183. doi:10.1111/j.1469-8749.2010.03665.x

24.

Erskine

H. E.

Ferrari

A. J.

Polanczyk

G. V.

Moffitt

T. E.

Murray

C. J.

Vos

. . . Scott

J. G.

(2014). The global burden of conduct disorder and attention-deficit/hyperactivity disorder in 2010. Journal of Child Psychology and Psychiatry and Allied Disciplines, 55, 328–336. doi:10.1111/jcpp.12186

25.

Fleming

Newham

(2017). Reliability of transcallosal inhibition in healthy adults. Frontiers in Human Neuroscience, 10, Article 681.

26.

Franzkowiak

Pollok

Biermann-Ruben

Sudmeyer

Paszek

Thomalla

. . . Schnitzler

(2012). Motor-cortical interaction in Gilles de la Tourette syndrome. PLoS ONE, 7(1), e27850. doi:10.1371/journal.pone.0027850

27.

Funabiki

Kawagishi

Uwatoko

Yoshimura

Murai

(2011). Development of a multi-dimensional scale for PDD and ADHD. Research in Developmental Disabilities, 32, 995–1003. doi:10.1016/j.ridd.2011.01.052

28.

Funke

Benali

(2011). Modulation of cortical inhibition by rTMS—Findings obtained from animal models. Journal of Physiology, 589(Pt. 18), 4423–4435. doi:10.1113/jphysiol.2011.206573

29.

Gaynes

B. N.

Lloyd

S. W.

Lux

Gartlehner

Hansen

R. A.

Brode

. . . Lohr

K. N.

(2014). Repetitive transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis. The Journal of Clinical Psychiatry, 75, 477–489. doi:10.4088/JCP.13r08815

30.

Gilliam

Stockman

Malek

Sharp

Greenstein

Lalonde

. . . Shaw

(2011). Developmental trajectories of the corpus callosum in attention-deficit/hyperactivity disorder. Biological Psychiatry, 69, 839–846. doi:10.1016/j.biopsych.2010.11.024

31.

Godar

S. C.

Mosher

L. J.

Di Giovanni

Bortolato

(2014). Animal models of tic disorders: A translational perspective. Journal of Neuroscience Methods, 238, 54–69. doi:10.1016/j.jneumeth.2014.09.008

32.

Gomez

Vidal

Maragoto

Morales

L. M.

Berrillo

Vera Cuesta

Robinson

(2017). Non-invasive brain stimulation for children with autism spectrum disorders: A short-term outcome study. Behavioral Science, 7(63), 1–12. doi:10.3390/bs7030063

33.

Gomez

Vidal

Morales

Baez

Maragoto

Galvizu

. . . Sanchez

(2014). Low frequency repetitive transcranial magnetic stimulation in children with attention deficit/hyperactivity disorder. Preliminary results. Brain Stimulation, 7, 760–762. doi:10.1016/j.brs.2014.06.001

34.

Goodman

D. W.

Starr

H. L.

Y. W.

Rostain

A. L.

Ascher

Armstrong

R. B.

(2017). Randomized, 6-week, placebo-controlled study of treatment for adult attention-deficit/hyperactivity disorder: Individualized dosing of Osmotic-Release Oral System (OROS) methylphenidate with a goal of symptom remission. Journal of Clinical Psychiatry, 78, 105–114. doi:10.4088/JCP.15m10348

35.

Green

Garg

(2018). Annual research review: The state of autism intervention science: Progress, target psychological and biological mechanisms and future prospects. Journal of Child Psychology and Psychiatry and Allied Disciplines, 59, 424–443. doi:10.1111/jcpp.12892

36.

Gurau

Bosl

W. J.

Newton

C. R.

(2017). How useful is electroencephalography in the diagnosis of autism spectrum disorders and the delineation of subtypes: A systematic review. Front Psychiatry, 8, Article 121. doi:10.3389/fpsyt.2017.00121

37.

Haber

S. N.

Knutson

(2010). The reward circuit: Linking primate anatomy and human imaging. Neuropsychopharmacology, 35(1), 4–26. doi:10.1038/npp.2009.129

38.

Hameed

M. Q.

Dhamne

S. C.

Gersner

Kaye

H. L.

Oberman

L. M.

Pascual-Leone

Rotenberg

(2017). Transcranial magnetic and direct current stimulation in children. Current Neurology and Neuroscience Reports, 17(2), Article 11. doi:10.1007/s11910-017-0719-0

39.

Hart

Radua

Nakao

Mataix-Cols

Rubia

(2013). Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: Exploring task-specific, stimulant medication, and age effects. Journal of the American Medical Association Psychiatry, 70, 185–198. doi:10.1001/jamapsychiatry.2013.277

40.

Lan

Mao

Chen

Huang

Pei

(2013). Frontoparietal regions may become hypoactive after intermittent theta burst stimulation over the contralateral homologous cortex in humans. Journal of Neurophysiology, 110, 2849–2856. doi:10.1152/jn.00369.2013

41.

Hirsch

L. E.

Pringsheim

(2016). Aripiprazole for autism spectrum disorders (ASD). The Cochrane Database of Systematic Reviews, 6, CD009043. doi:10.1002/14651858.CD009043.pub3

42.

Huang

Y.-Z.

Sommer

Thickbroom

Hamada

Pascual-Leonne

Paulus

. . . Ugawa

(2009). Consensus: New methodologies for brain stimulation. Brain Stimulation, 2(1), 2–13. doi:10.1016/j.brs.2008.09.007

43.

Jarbo

Verstynen

T. D.

(2015). Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum. Journal of Neuroscience, 35, 3865–3878. doi:10.1523/JNEUROSCI.2636-14.2015

44.

Kaller

C. P.

Reisert

Katzev

Umarova

Mader

Hennig

. . . Kostering

(2015). Predicting planning performance from structural connectivity between left and right mid-dorsolateral prefrontal cortex: Moderating effects of age during postadolescence and midadulthood. Cerebral Cortex, 25, 869–883. doi:10.1093/cercor/bht276

45.

Klein

Onnink

van Donkelaar

Wolfers

Harich

Shi

. . . Franke

(2017). Brain imaging genetics in ADHD and beyond–Mapping pathways from gene to disorder at different levels of complexity. Neuroscience and Biobehavioral Reviews, 80, 115–155. doi:10.1016/j.neubiorev.2017.01.013

46.

Kohls

Yerys

B. E.

Schultz

R. T.

(2014). Striatal development in autism: Repetitive behaviors and the reward circuitry. Biological Psychiatry, 76, 358–359. doi:10.1016/j.biopsych.2014.07.010

47.

Kral

Lally

Boan

(2017). Effectiveness and side effect profile of stimulant medication for the treatment of attention-deficit/hyperactivity disorder in youth with epilepsy. Journal of Child and Adolescent Psychopharmacology, 27, 735–740.

48.

Krishnan

Santos

Peterson

M. D.

Ehinger

(2015). Safety of noninvasive brain stimulation in children and adolescents. Brain Stimulation, 8, 76–87. doi:10.1016/j.brs.2014.10.012

49.

Kwon

H. J.

Lim

W. S.

Lim

M. H.

Lee

S. J.

Hyun

J. K.

Chae

J. H.

Paik

K. C.

(2011). 1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette’s syndrome. Neuroscience Letters, 492(1), 1–4. doi:10.1016/j.neulet.2011.01.007

50.

Landeros-Weisenberger

Mantovani

Motlagh

Alvarenga

Katsovich

Leckman

Lisanby

(2015). Randomized sham controlled double-blind trial of repetitive transcranial magnetic stimulation for adults with severe Tourette syndrome. Brain Stimulation, 8, 574–581.

51.

Langen

Bos

Noordermeer

S. D.

Nederveen

van Engeland

Durston

(2014). Changes in the development of striatum are involved in repetitive behavior in autism. Biological Psychiatry, 76, 405–411. doi:10.1016/j.biopsych.2013.08.013

52.

Larsson

Lichtenstein

Larsson

J. O.

(2006). Genetic contributions to the development of ADHD subtypes from childhood to adolescence. Journal of the American Academy of Child and Adolescent Psychiatry, 45, 973–981. doi:10.1097/01.chi.0000222787.57100.d8

53.

Lefaucheur

J. P.

Andre-Obadia

Antal

Ayache

S. S.

Baeken

Benninger

D. H.

. . . Garcia-Larrea

(2014). Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clinical Neurophysiology, 125, 2150–2206. doi:10.1016/j.clinph.2014.05.021

54.

Liu

Miao

Wang

Gao

Yin

Zhang

. . . Peng

(2013). Structural abnormalities in early Tourette syndrome children: A combined voxel-based morphometry and tract-based spatial statistics study. PLoS ONE, 8(9), e76105. doi:10.1371/journal.pone.0076105

55.

Lozeron

Poujois

Richard

Masmoudi

Meppiel

Woimant

Kubis

(2016). Contribution of TMS and rTMS in the understanding of the pathophysiology and in the treatment of Dystonia. Frontiers in Neural Circuits, 10, Article 90.

56.

Maia

T. V.

Conceicao

V. A.

(2017). The roles of phasic and tonic dopamine in tic learning and expression. Biological Psychiatry, 82, 401–412. doi:10.1016/j.biopsych.2017.05.025

57.

McDougle

Holmes

Carlson

Pelton

Cohen

Price

L. A.

(1998). A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Archives of General Psychiatry, 55, 633–641.

58.

Miyamoto

Duncan

G. E.

Marx

C. E.

Lieberman

J. A.

(2005). Treatments for schizophrenia: A critical review of pharmacology and mechanisms of action of antipsychotic drugs. Molecular Psychiatry, 10, 79–104. doi:10.1038/sj.mp.4001556

59.

Moher

Liberati

Tetzlaff

Altman

D. G.

PRISMA Group. (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Journal of Clinical Epidemiology, 62, 1006–1012. doi:10.1016/j.jclinepi.2009.06.005

60.

Münchau

Bloem

Thilo

Trimble

Rothwell

Robertson

(2002). Repetitive transcranial magnetic stimulation for Tourette syndrome. Neurology, 59, 1789–1791.

61.

Neely

Garcia

Bankston

Green

(2018). Generalization and maintenance of functional communication training for individuals with developmental disabilities: A systematic and quality review. Research in Developmental Disabilities, 79, 116–129. doi:10.1016/j.ridd.2018.02.002

62.

Noda

Zomorrodi

Vila-Rodriguez

Downar

Farzan

Cash

R. F. H.

. . . Blumberger

D. M.

(2018). Impaired neuroplasticity in the prefrontal cortex in depression indexed through paired associative stimulation. Depression and Anxiety, 35, 448–456. doi:10.1002/da.22738

63.

Noriuchi

Kikuchi

Yoshiura

Kira

Shigeto

Hara

. . . Kamio

(2010). Altered white matter fractional anisotropy and social impairment in children with autism spectrum disorder. Brain Research, 1362, 141–149. doi:10.1016/j.brainres.2010.09.051

64.

Oberman

L. M.

Enticott

P. G.

Casanova

M. F.

Rotenberg

Pascual-Leone

McCracken

J. T.

TMS in ASD Consensus Group. (2016). Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research. Autism Research, 9, 184–203. doi:10.1002/aur.1567

65.

Oberman

L. M.

Ifert-Miller

Najib

Bashir

Heydrich

J. G.

Picker

. . . Pascual-Leone

(2016). Abnormal Mechanisms of plasticity and metaplasticity in autism spectrum disorders and fragile X syndrome. Journal of Child and Adolescent Psychopharmacology, 26, 617–624. doi:10.1089/cap.2015.0166

66.

Oberman

L. M.

Pascual-Leone

(2014). Hyperplasticity in autism spectrum disorder confers protection from Alzheimer’s disease. Medical Hypotheses, 83, 337–342. doi:10.1016/j.mehy.2014.06.008

67.

Oberwelland

Schilbach

Barisic

Krall

S. C.

Vogeley

Fink

G. R.

. . . Schulte-Ruther

(2017). Young adolescents with autism show abnormal joint attention network: A gaze contingent fMRI study. NeuroImage, 14, 112–121. doi:10.1016/j.nicl.2017.01.006

68.

O’Reardon

J. P.

Solvason

H. B.

Janicak

P. G.

Sampson

Isenberg

K. E.

Nahas

. . . Sackeim

H. A.

(2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biological Psychiatry, 62, 1208–1216. doi:10.1016/j.biopsych.2007.01.018

69.

Orth

Kirby

Richardson

M. P.

Snijders

A. H.

Rothwell

J. C.

Trimble

M. R.

. . . Munchau

(2005). Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome. Clinical Neurophysiology, 116, 764–768. doi:10.1016/j.clinph.2004.10.003

70.

Panerai

Tasca

Lanuzza

Trubia

Ferri

Musso

. . . Elia

(2014). Effects of repetitive transcranial magnetic stimulation in performing eye-hand integration tasks: Four preliminary studies with children showing low-functioning autism. Autism, 18, 638–650. doi:10.1177/1362361313495717

71.

Park

H. R.

Lee

J. M.

Moon

H. E.

Lee

D. S.

Kim

B. N.

Kim

. . . Paek

S. H.

(2016). A short review on the current understanding of autism spectrum disorders. Experimental Neurobiology, 25(1), 1–13. doi:10.5607/en.2016.25.1.1

72.

Peterson

Staib

Scahill

Zhang

Anderson

Leckman

. . . Webster

(2001). Regional brain and ventricular volumes in Tourette syndrome. Archives of General Psychiatry, 58, 427–440.

73.

Philipsen

Jans

Graf

Matthies

Borel

Colla

Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS) Consortium. (2015). Effects of group psychotherapy, individual counseling, methylphenidate, and placebo in the treatment of adult attention-deficit/hyperactivity disorder: A randomized clinical trial. Journal of the American Academy of Child and Adolescent Psychiatry, 72, 1199–1210. doi:10.1001/jamapsychiatry.2015.2146

74.

Rubia

Smith

A. B.

Brammer

M. J.

Taylor

(2007). Temporal lobe dysfunction in medication-naive boys with attention-deficit/hyperactivity disorder during attention allocation and its relation to response variability. Biological Psychiatry, 62, 999–1006. doi:10.1016/j.biopsych.2007.02.024

75.

Sanchez-Valle

Posada

Villaverde-Hueso

Tourino

Ferrari-Arroyo

M. J.

Boada

. . . Fuentes-Biggi

(2008). Estimating the burden of disease for autism spectrum disorders in Spain in 2003. Journal of Autism and Developmental Disorders, 38, 288–296. doi:10.1007/s10803-007-0393-1

76.

Savolainen

Eisman

Mason

W. A.

Schwartz

J. A.

Miettunen

Jarvelin

M. R.

(2018). Socioeconomic disadvantage and psychological deficits: Pathways from early cumulative risk to late-adolescent criminal conviction. Journal of Adolescence, 65, 16–24. doi:10.1016/j.adolescence.2018.02.010

77.

Scharf

J. M.

Miller

L. L.

Gauvin

C. A.

Alabiso

Mathews

C. A.

Ben-Shlomo

(2015). Population prevalence of Tourette syndrome: A systematic review and meta-analysis. Movement Disorders, 30, 221–228. doi:10.1002/mds.26089

78.

Shang

C. Y.

Pan

Y. L.

Lin

H. Y.

Huang

L. W.

Gau

S. S.

(2015). An open-label, randomized trial of methylphenidate and atomoxetine treatment in children with attention-deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology, 25, 566–573. doi:10.1089/cap.2015.0035

79.

Shaw

Eckstrand

Sharp

Blumenthal

Lerch

Greenstein

. . . Rapoport

(2007). Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences of the United States of America, 104, 19649–19654.

80.

Silton

R. L.

Heller

Towers

D. N.

Engels

A. S.

Spielberg

J. M.

Edgar

J. C.

. . . Miller

G. A.

(2010). The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control. NeuroImage, 50, 1292–1302. doi:10.1016/j.neuroimage.2009.12.061

81.

Singer

Minzer

(2003). Neurobiology of Tourette’s syndrome: Concepts of neuroanatomic localization and neurochemical abnormalities. Brain & Development, 25(Suppl. 1), S70–S84.

82.

Sokhadze

E. M.

Baruth

J. M.

Sears

Sokhadze

G. E.

El-Baz

A. S.

Casanova

M. F.

(2012). Prefrontal neuromodulation using rTMS improves error monitoring and correction function in autism. Applied Psychophysiology and Biofeedback, 37, 91–102. doi:10.1007/s10484-012-9182-5

83.

Sokhadze

E. M.

Baruth

J. M.

Tasman

Mansoor

Ramaswamy

Sears

M. F.

(2010). Low-frequency repetitive transcranial magnetic stimulation (rTMS) affects event-related potential measures of novelty processing in autism. Applied Psychophysiology and Biofeedback, 35, 147–161. doi:10.1007/s10484-009-9121-2

84.

Sokhadze

E. M.

El-Baz

A. S.

Sears

L. L.

Opris

Casanova

M. F.

(2014). rTMS neuromodulation improves electrocortical functional measures of information processing and behavioral responses in autism. Frontiers in Systems Neuroscience, 8, Article 134. doi:10.3389/fnsys.2014.00134

85.

Sokhadze

E. M.

El-Baz

A. S.

Tasman

Sears

L. L.

Wang

Lamina

E. V.

Casanova

M. F.

(2014). Neuromodulation integrating rTMS and neurofeedback for the treatment of autism spectrum disorder: An exploratory study. Applied Psychophysiology and Biofeedback, 39, 237–257. doi:10.1007/s10484-014-9264-7

86.

Stanford

A. D.

Luber

Unger

Cycowicz

Y. M.

Malaspina

Lisanby

S. H.

(2013). Single pulse TMS differentially modulates reward behavior. Neuropsychologia, 51, 3041–3047. doi:10.1016/j.neuropsychologia.2013.09.016

87.

Stern

Silbersweig

Chee

Holmes

Robertson

Trimble

. . . Dolan

(2000). A functional neuroanatomy of tics in Tourette syndrome. Archives of General Psychiatry, 57, 741–748.

88.

Storebo

O. J.

Ramstad

Krogh

H. B.

Nilausen

T. D.

Skoog

Holmskov

Gluud

(2015). Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). The Cochrane Database of Systematic Reviews, 11, CD009885. doi:10.1002/14651858.CD009885.pub2

89.

Strafella

A. P.

Paus

Barrett

Dagher

(2001). Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. Journal of Neuroscience, 21, RC157.

90.

Strafella

A. P.

Paus

Fraraccio

Dagher

(2003). Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain, 126(Pt. 12), 2609–2615. doi:10.1093/brain/awg268

91.

Suppa

Huang

Y. Z.

Funke

Ridding

M. C.

Cheeran

Di Lazzaro

. . . Rothwell

J. C.

(2016). Ten Years of theta burst stimulation in humans: Established knowledge, unknowns and prospects. Brain Stimulation, 9, 323–335. doi:10.1016/j.brs.2016.01.006

92.

Torres

Goyal

Burke-Aaronson

Gay

Lee

(2017). Patterns of symptoms of perinatal depression and stress in late adolescent and young adult mothers. Journal of Obstetric, Gynecologic, and Neonatal Nursing, 46, 814–823.

93.

Uddin

L. Q.

Supekar

Lynch

C. J.

Khouzam

Phillips

Feinstein

. . . Menon

(2013). Salience network-based classification and prediction of symptom severity in children with autism. Journal of the American Academy of Child and Adolescent Psychiatry, 70, 869–879. doi:10.1001/jamapsychiatry.2013.104

94.

Uddin

L. Q.

Supekar

Menon

(2013). Reconceptualizing functional brain connectivity in autism from a developmental perspective. Frontiers in Human Neuroscience, 7, Article 458. doi:10.3389/fnhum.2013.00458

95.

U.S. Environmental Protection Agency. (2017). America’s children and the environment (3rd ed.). Washington, DC: Author.

96.

Vattikuti

Chow

C. C.

(2010). A computational model for cerebral cortical dysfunction in autism spectrum disorders. Biological Psychiatry, 67, 672–678. doi:10.1016/j.biopsych.2009.09.008

97.

Virues-Ortega

Julio

F. M.

Pastor-Barriuso

(2013). The TEACCH program for children and adults with autism: A meta-analysis of intervention studies. Clinical Psychology Review, 33, 940–953. doi:10.1016/j.cpr.2013.07.005

98.

Wang

Hensley

M. K.

Tasman

Sears

Casanova

M. F.

Sokhadze

E. M.

(2016). Heart rate variability and skin conductance during repetitive TMS course in children with autism. Applied Psychophysiology and Biofeedback, 41, 47–60. doi:10.1007/s10484-015-9311-z

99.

Weaver

Rostain

A. L.

Mace

Akhtar

Moss

O’Reardon

J. P.

(2012). Transcranial magnetic stimulation (TMS) in the treatment of attention-deficit/hyperactivity disorder in adolescents and young adults: A pilot study. The Journal of ECT, 28, 98–103. doi:10.1097/YCT.0b013e31824532c8

100.

Weisman

Qureshi

I. A.

Leckman

J. F.

Scahill

Bloch

M. H.

(2013). Systematic review: Pharmacological treatment of tic disorders–efficacy of antipsychotic and alpha-2 adrenergic agonist agents. Neuroscience & Biobehavioral Reviews, 37, 1162–1171. doi:10.1016/j.neubiorev.2012.09.008

101.

S. W.

Maloney

Gilbert

D. L.

Dixon

S. G.

Horn

P. S.

Huddleston

D. A.

. . . Vannest

(2014). Functional MRI-navigated repetitive transcranial magnetic stimulation over supplementary motor area in chronic tic disorders. Brain Stimulation, 7, 212–218. doi:10.1016/j.brs.2013.10.005

102.

Zhang

Kutyifa

Moss

A. J.

McNitt

Zareba

Kaufman

E. S.

(2015). Long-QT syndrome and therapy for attention deficit/hyperactivity disorder. Journal of Cardiovascular Electrophysiology, 26, 1039–1044. doi:10.1111/jce.12739

103.

Zheng

Zhang

(2015). Synaptic plasticity-related neural oscillations on hippocampus-prefrontal cortex pathway in depression. Neuroscience, 292, 170–180. doi:10.1016/j.neuroscience.2015.01.071

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.50 MB

0.32 MB