Restoration of disturbed intracortical motor inhibition and facilitation in attention deficit hyperactivity disorder children by methylphenidate.

BACKGROUND: Previous investigations using transcranial magnetic stimulation (TMS) have shown that neural inhibitory motor circuits are disturbed in ADHD children. We sought to investigate the influence of methylphenidate (MPH) on inhibitory and facilitatory motor circuits of ADHD children with TMS paired pulse protocols using surplus long interval inter-stimulus intervals (ISI) not investigated so far. METHODS: Motorcortical modulation was tested with TMS paired pulse protocols employing ISI of 3, 13, 50, 100, 200, and 300 msec in 18 ADHD children before and on treatment with MPH. Clinical improvement by MPH was measured by the Conners score. RESULTS: Analysis of variance (ANOVA) revealed a significant three-way interaction "Group x Amplitude x ISI," p = .001. Subsequent two-factorial ANOVAs and t-tests showed group specific differences of motor evoked potential (MEP) amplitudes for inhibitory ISIs of 3 and 100 msec, and for facilitatory ISIs of 13 and 50 msec. Compared to controls, an adjustment of these parameters by MPH could be shown. On MPH, a significant bivariate correlation was found between the Conners score reduction and averaged MEP amplitude changes only for inhibitory ISIs (3 and 100 msec). CONCLUSIONS: In ADHD children, MPH modulates disturbed facilitatory and inhibitory motor circuits, which for the latter is associated with clinical improvement.     

Impaired transcallosally mediated motor inhibition in adults with attention-deficit/hyperactivity disorder is modulated by methylphenidate

Using transcranial magnetic stimulation (TMS) in children with ADHD, an impaired transcallosally mediated motor inhibition (ipsilateral silent period, iSP) was found, and its restoration was correlated with improvement of hyperactivity under medication with methylphenidate (MPH). Hyperactivity has been reported to decrease during transition into adulthood, although some motor dysfunction might persist. As one underlying neurophysiological process, a development-dependent normalization of motor cortical excitability might be postulated. In order to test this hypothesis, we measured the iSP in 21 adult ADHD patients and twenty-one sex- and age-matched healthy controls. In 16 of these patients, a second TMS was performed under treatment with MPH. Our results indicate a persistence of impaired transcallosally mediated motor cortical inhibition (shortened duration) in ADHD adults, which was correlated with clinical characteristics of hyperactivity and restlessness, and was restored by MPH. In contrast to ADHD in childhood, the iSP latency was not impaired, suggesting a partial development-dependent normalization of motor cortical excitability in ADHD adults. ISP duration appears to be a sensitive parameter for the assessment of disturbed intercortical inhibition in adults with ADHD.     

The variability of intracortical inhibition and facilitation

OBJECTIVE: To assess the variability of transcranial magnetic stimulation paired pulse measurements of cortical excitability between subjects, between sessions and within subjects within sessions. METHODS: In experiment 1, intracortical inhibition and facilitation were assessed with a fixed conditioning stimulus intensity (CSI) of 80% of active motor threshold (AMT) whereas in experiment 2, the effect of different CSIs (60-110% of AMT) was investigated. RESULTS: Experiment 1 revealed that subjects differed significantly in the degree of inhibition and facilitation. Between sessions the variability was substantial as predicted by high within session variability. Experiment 2 allowed determination of individual thresholds for inhibition and facilitation. These thresholds were the best predictor of the amount of inhibition or facilitation at a given CSI. Across subjects we observed a high correlation of the threshold for inhibition (expressed in terms of maximum stimulator output) with AMT (r=0.93). Results for facilitation were more variable. CONCLUSIONS: The variability was high if a single CSI was used to compare the percent intracortical inhibition or facilitation between subjects, or between sessions. Much less variable was the threshold for intracortical inhibition/facilitation, which was highly correlated to AMT. We suggest that the ratio of CSI:AMT is a robust and useful additional measure of the integrity of neuronal circuits underlying intracortical inhibition/facilitation.     

Intracortical inhibition and facilitation are impaired in patients with early Parkinson''s disease: a paired TMS study

Twelve patients with early Parkinson's disease (PD), none of whom had received any previous L-DOPA treatment, but using other antiparkinsonian drugs, were studied using transcranial magnetic stimulation (TMS). Contralateral and ipsilateral hemispheres were examined, with a focus on the more pronounced parkinsonian symptoms. The conditioning-test TMS paradigm (with a subthreshold conditioning stimulus and a suprathreshold test stimulus) was used through a stimulating round coil. Paired stimuli of short (3, 5 and 7 ms), medium (10, 15 and 20 ms), and long (100, 150, 200 and 250 ms) interstimulus intervals (ISI) were pseudo-randomly mixed with a single stimulus. The first interosseus muscle was used for the motor-evoked potential recordings. Ten healthy subjects (age and sex matched) were studied in the same manner to obtain normative data. When both groups were compared, the significant difference (reduction of the intracortical inhibition and facilitation) between the PD patients and the control group was found at the short and the medium ISI (3, 5, 7, 10, 15 and 20 ms) in both hemispheres (P < 0.05). The longer ISI produced non-significant differences between the two groups in intracortical excitability. There was a non-significant difference in the motor threshold. In conclusion, it can be supposed that both intracortical inhibition and facilitation are impaired in patients with early PD using other antiparkinsonian treatments than L-DOPA or dopamine agonists.     

Psychotherapy of attention deficit hyperactivity disorder in adults

In clinical practice many adult patients with attention deficit hyperactivity disorder (ADHD) ask for an additional psychotherapeutic intervention besides the medical therapy. In this paper we present a structured skill training program particularly tailored for adult patients with ADHD. The program is based on the principles of cognitive-behavioral treatment for borderline personality disorder developed by M. Linehan. It was modified to suit the special needs of adult patients with ADHD. In this exploratory pilot study we tested this program in a group setting. The following elements were presented: neurobiology of ADHD, mindfulness, chaos and control, behavior analysis, emotion regulation, depression, medication in ADHD, impulse control, stress management, dependency, ADHD in relationship and self respect. In an open study design patients were assessed clinically using psychometric scales (Attention Deficit Hyperactivity Disorder Checklist according to DSM-IV, 16 items of the SCL-90-R, Beck-Depression Inventory, visual analogue scale) prior to and following group therapy. This treatment resulted in positive outcomes in that patients improved on all psychometric scales. Received: 19 April 2002 / Accepted: 18 July 2002     

Hyperactivity in motor response inhibition networks in unmedicated children with attention deficit-hyperactivity disorder

Objectives: Hypo/reduced activity in motor response inhibition (RI) cerebral networks was recently proposed as a promising specific neurobiological marker of attention deficit-hyperactivity disorder (ADHD). Before adopting such a pattern as a key diagnosis tool, we aim to replicate in an independent study the mechanisms underlying reduced RI-related activity in ADHD, after controlling for potentially confounding effects.

Methods: In this fMRI study, we investigated the neural networks mediating successful and failed motor RI in children with ADHD and typically developing children (TDC) using the stop-signal task (SST) paradigm.

Results: In contrast to hypofrontality predictions, children with ADHD exhibit increased neural activity during successful response inhibition in an RI-related brain network encompassing the indirect and/or hyperdirect pathways between the basal ganglia and cortex. Voxel-based morphometry analyses have further evidenced reduced grey matter volume in the left caudate in children with ADHD, which paralleled higher functional responses. Finally, connectivity analyses disclosed tighter coupling between a set of cortical regions and the right caudate as well as the right IFG, networks involved in successful RI.

Conclusions: Hypo/reduced activity in RI cerebral networks in children with ADHD cannot at this time be considered as a systematic biomarker for ADHD.     

Gait in attention deficit hyperactivity disorder

Abstract Background Cognitive function and the loading of attention presumably play an important role in gait as well as in fall risk, but previous work has not demonstrated this in any cause-and-effect way. Objectives To gain insight into the relationship between gait and cognitive function, we sought: (1) To compare the gait rhythmicity (stride time variability) of children with attention deficit hyperactivity disorder (ADHD) to controls, (2) To test the hypothesis that dual tasking leads to increased stride-to-stride variability in ADHD, and (3) To test whether pharmacological treatment that relieves ADHD symptoms reduces stride-to-stride variability. Patients and Methods Gait was quantified in children with ADHD and in age-matched healthy controls under single task and dual task conditions on three occasions: off medications (both groups) and, in the ADHD group, after double blinded, randomized administration of methylphenidate (MPH) or placebo. Results At baseline, children with ADHD tended to walk with increased stride-to-stride variability compared to the controls during the single task condition (p = 0.09). During dual task walking, stride time variability was significantly reduced in the children with ADHD (p < 0.004), but not in the controls. In the children with ADHD, the placebo did not significantly affect stride-to-stride variability or the dual tasking response. In contrast, stride time variability was significantly reduced on MPH (p < 0.001) such that dual tasking no longer affected variability. Conclusions The present findings demonstrate alterations in the gait of children with ADHD, support a cause and effect link between cognitive function and gait, and suggest that enhancement of attention abilities may, in certain populations, improve gait rhythmicity.     

Intracortical inhibition and facilitation upon awakening from different sleep stages: a transcranial magnetic stimulation study

Intracortical facilitation and inhibition, as assessed by the paired-pulse transcranial magnetic stimulation technique with a subthreshold conditioning pulse followed by a suprathreshold test pulse, was studied upon awakening from REM and slow-wave sleep (SWS). Ten normal subjects were studied for four consecutive nights. Intracortical facilitation and inhibition were assessed upon awakening from SWS and REM sleep, and during a presleep baseline. Independently of sleep stage at awakening, intracortical inhibition was found at 1-3-ms interstimulus intervals and facilitation at 7-15-ms interstimulus intervals. Motor thresholds were higher in SWS awakenings, with no differences between REM awakenings and wakefulness, while motor evoked potential amplitude to unconditioned stimuli decreased upon REM awakening as compared to the other conditions. REM sleep awakenings showed a significant increase of intracortical facilitation at 10 and 15 ms, while intracortical inhibition was not affected by sleep stage at awakening. While the dissociation between motor thresholds and motor evoked potential amplitudes could be explained by the different excitability of the corticospinal system during SWS and REM sleep, the heightened cortical facilitation upon awakening from REM sleep points to a cortical motor activation during this stage.     

Transferrin in korean children with attention deficit hyperactivity disorder

Objective

The aim of the present study was to investigate the relationship between iron, ferritin, transferrin, total iron binding capacity (TIBC), hemoglobin, mean corpuscular volume (MCV) mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in children with ADHD.

Methods

MethodsaaThe sample consisted of 48 ADHD children and sex and age matched control children (a couple of 28 boys, 22 girls; age 6-8 years; mean±SD, 6.98±0.39). We diagnosed ADHD according to DSM-IV. ADHD symptoms were evaluated subjectively with Conners'' Parent Rating Scales, Dupaul Parent ADHD Rating Scales. Subjects with ADHD and control were evaluated the hematology test including the iron, transferrin, MCV etc. Paired t test were used to evaluate the relation of a lot of hematology findings between ADHD and control group.

Results

The serum iron, ferritin, transferrin, TIBC, hemoglobin, MCV, MCH, and MCHC of ADHD group were respectively 80.92±33.33 ug/dL, 35.81±16.59 ng/mL, 248.42±44.15 mg/dL, 351.69±102.13 ug/dL, 12.78±0.71 g/dL, 82.94±2.58 fL, 27.18±1.12 uug, 32.79±1.12%. Otherwise the serum iron, ferritin, transferrin, TIBC, hemoglobin, MCV, MCH, and MCHC of control group were respectively 82.04±28.14 ug/dL, 37.05±18.28 ng/mL, 266.27±25.40 mg/dL, 352.77±89.54 ug/dL, 12.77±0.70 g/dL, 81.81±2.96 fL, 26.69±0.99 uug, 32.66±0.96%. A significant difference were found in the transferrin(t=2.63, p=0.011), MCV (t=2.19, p=0.034), and MCH (t=2.18, p=0.034).

Conclusion

These results suggested that lower transferrin levels might be related with ADHD symptoms.     

Atomoxetine improved response inhibition in adults with attention deficit/hyperactivity disorder.

BACKGROUND: Atomoxetine, a highly selective noradrenaline reuptake inhibitor (SNRI), shows efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD). Compared with psychostimulants, atomoxetine has a distinct mode of brain action and potentially lower addictive potential. Studies have yet to assess whether atomoxetine improves cognition following a single oral dose in ADHD. METHODS: Twenty-two adults with DSM-IV ADHD were administered a single oral dose of atomoxetine (60 mg) in a placebo-controlled double-blind crossover design. Cognitive effects were assessed using stop-signal, sustained attention, spatial working memory, and set-shifting paradigms. Normative cognitive data from 20 healthy volunteers were collected for comparison. RESULTS: The ADHD patients under placebo conditions showed response inhibition and working memory deficits compared with healthy volunteers. Atomoxetine treatment in the ADHD patients was associated with shorter stop-signal reaction times and lower numbers of commission errors on the sustained attention task. CONCLUSIONS: Atomoxetine improved inhibitory control, most likely via noradrenergically mediated augmentation of prefrontal cortex function. These results have implications for understanding the mechanisms by which atomoxetine exerts beneficial clinical effects and suggest novel treatment directions for other disorders of impulsivity.     

Sustained attention in sensory modulation disorder and attention deficit/hyperactivity disorder

BackgroundThere are high comorbidity rates between sensory modulation disorder (SMD) and attention deficit hyperactivity disorder (ADHD). Knowledge regarding the objective neuropsychological differentiation between them is scarce.AimThis study examines the effects of SMD and ADHD on a sustained attention task with and without aversive auditory conditions.MethodSixty six young adult females were tested on the Conjunctive - Continuous Performance Task-Visual (CCPT-V) measuring sustained attention, under two conditions: 1) aversive condition (with the three most aversive sounds chosen by the participant), and 2) non-aversive condition (without sounds).ResultsBoth the SMD and ADHD factors exhibited performance deficits in the sustained attention task. All study participants performed worse on both sustained attention and speed of processing when aversive sounds were present.ConclusionWe conclude that impaired sustained attention cannot differentiate between SMD and ADHD. Hence, these results should be taken under consideration in the assessment process of ADHD vs. SMD.     

Fronto-striatal underactivation during interference inhibition and attention allocation in grown up children with attention deficit/hyperactivity disorder and persistent symptoms

Attention deficit hyperactivity disorder (ADHD) in medication-naïve children has been associated with reduced activation in inferior/medial prefrontal, striatal and parieto-temporal cortices during inhibitory control and attention allocation. Functional magnetic resonance imaging (fMRI) studies in adult ADHD, however, have been inconsistent and confounded by medication-history and the need for a retrospective diagnosis of childhood ADHD. We used fMRI combined with a Simon task that measured interference inhibition and controlled for and co-measured attention allocation to compare brain function in 11 medication-naïve adults with persistent inattentive/hyperactive behaviours, followed up from childhood ADHD, and 15 age-matched controls. Despite comparable task performance, patients showed reduced activation compared to controls in left orbital/medial frontal cortex and striatum during interference inhibition and in left lateral inferior/dorsolateral prefrontal cortex during attention allocation. Whole-brain regression analyses within patients showed a negative correlation between symptom severity and fronto-striatal, temporo-parietal and cerebellar brain activation. The findings demonstrate that the typical fronto-striatal dysfunction observed in children with ADHD during interference inhibition and attention allocation is also observed in adults grown up from childhood ADHD with persistent symptoms. Furthermore, they show that functional deficits in adult ADHD are not related to chronic stimulant medication given that this sample was medication-naive.     

H-MR-spectroscopy of cerebellum in adult attention deficit/hyperactivity disorder

Introduction

Neurobiological research has implicated the cerebellum as one possible site of neurophysiological dysfunction in ADHD. Latest theoretical conceptualizations of the cerebellum as core site of the brain to model motor as well as cognitive behavior puts further weight to the assumption that it might play a key role in ADHD pathophysiology.

Methods

30 medication free adult ADHD patients and 30 group matched (gender, age and education) healthy controls were investigated using the method of chemical shift imaging (CSI) of the cerebellum. The vermis, left and right cerebellar hemispheres were processed separately.

Results

We found significantly increased glutamate-glutamine (Glx) to creatine (Cre) ratios in the left cerebellar hemisphere. No other differences in measured metabolite concentrations were observed.

Discussion

To our knowledge this is the first evidence for neurochemical alterations in cerebellar neurochemistry in adult ADHD. They relate well to recent hypotheses that the cerebellum might control mental activities by internal models.     

Attention deficit hyperactivity disorder in adults

Abstract

Objective. To examine available literature regarding attention deficit hyperactivity disorder (ADHD) in adults. Methods. An electronic literature search of peer-reviewed English language articles using MEDLINE (without time limits) was undertaken. Results. Symptoms of ADHD in adults exert a substantial negative impact on daily life, including work, social life and relationships. Co-morbidities are common, further impairing quality of life. Diagnosis of adult ADHD can be difficult, as current criteria require evidence of symptom onset before the age of 7 years and impact on activities typically undertaken by children. Drug therapy is the first-line treatment for adult ADHD, particularly stimulant medication. However, methylphenidate (MPH) immediate-release tablets require three or more times daily dosing, which can impact on compliance, while demonstrating a loss of symptomatic benefit later in the day. Extended-release preparations of MPH, mixed amphetamine salts and dexamphetamine can provide symptom control for 6–12 h and the non-stimulant atomoxetine has demonstrated benefit in reducing ADHD symptoms. These therapies are generally well tolerated, but may be associated with adverse effects on the cardiovascular system, which need to be further assessed in controlled clinical trials. Psychological therapy may be beneficial in adults who continue to experience clinically significant symptoms while receiving pharmacotherapy. Conclusion. Further research in all areas of adult ADHD is urgently needed.     

Smell identification function in children with attention deficit hyperactivity disorder

Objective

Deficits in olfactory function are common features in neurodegenerative and neuropsychiatric disorders. Olfactory processing is related to dopamine metabolism and orbitofrontal cortex functioning, both known to be involved in the neurobiology of ADHD. Some investigations suggested alterations in olfactory processing (identification and detection threshold) in patients with ADHD. Despite increasing knowledge, controversy about this topic still exists regarding children with ADHD. This study was conducted to help elucidate some of this controversy.

Methods

50 participants (8-15 years, mean=10.70±1.77) with ADHD were compared to 50 controls. The two groups were well matched for age, gender and Mean School Scores (MSS). We assessed odor identification and threshold through a smell test composed of two tests of identification and detection threshold. Odor detection threshold was assessed with the odorant phenyl ethyl alcohol solved in propylene glycol using a single staircase method. Odor identification was assessed with chemical essences of five common odorants.

Results

The mean Sensory Identification Score for children with ADHD and the control groups were 3.76 (1.06) and 4.46 (0.76), respectively (p<0.001). The mean for Sensory Threshold Score for ADHD and control group was 6.4 (3.35) and 9.75 (2.16), respectively (p<0.001).

Conclusion

This study replicated altered olfactory performance in ADHD. Substantial olfactory deficits across the two domains of identification and detection threshold are observed in children with ADHD. These deficits do not seem to be a result of olfactory task difficulty and are not influenced by age, gender and MSS. Further studies are required to investigate whether olfactory function can be used as a biological marker for early diagnosis, treatment and prognosis of ADHD.     

An examination of the effects of stimulant medication on response inhibition: a comparison between children with and without attention deficit hyperactivity disorder

This study investigated whether methylphenidate is effective in improving response inhibition in children with Attention Deficit Hyperactivity Disorder (ADHD). Children with ADHD were compared with normally developing children on measures of response inhibition. Participants with ADHD were compared across two conditions - medicated and unmedicated. There was no significant difference between the inhibitory control of children with and without ADHD. Children with ADHD showed significant improvements in inhibitory control following methylphenidate. The findings of the present study contrast with previous studies which document reduced inhibitory control in ADHD, compared with normally developing children. Reports of methylphenidate improving functioning in children with ADHD are supported. Limitation and implications of the study are discussed.     

Excessive daytime sleepiness in adults with possible attention deficit/hyperactivity disorder (ADHD): a web-based cross-sectional study

ObjectivesArousal dysregulation has been speculated to be involved in the pathological mechanism of attention deficit/hyperactivity disorder (ADHD). However, there has been no epidemiological study assessing the real condition of excessive daytime sleepiness (EDS) in adults with ADHD. This study investigated the prevalence of EDS and the relationship between sleepiness and ADHD symptoms in adults with possible ADHD.MethodsAn observational, cross-sectional, web-based study was performed. Participants were 9822 Japanese adults aged 20–69 years who completed an Internet-based questionnaire that assessed ADHD symptoms, autistic traits, depressive symptoms, chronotype, sleepiness, and sleep disturbances.ResultsParticipants with possible ADHD were more likely than non-ADHD participants to have an evening chronotype and experience depressive symptoms, sleepiness, and sleep disturbances. The rates of having moderate and severe sleepiness in the possible ADHD group were higher than those in the non-ADHD group. Hierarchical logistic regression analyses revealed that the presence of ADHD symptoms was independently associated with EDS even after adjusting for factors related to the presence of sleepiness. When examining inattention and hyperactivity scores among participants with possible ADHD, the inattention score was significantly higher in the severe EDS group compared with the moderate and non-EDS groups.ConclusionsEDS was relatively common in adults with possible ADHD. ADHD symptoms, especially inattentiveness, were associated with the formation of EDS in this population.     

Schizotypy, attention deficit hyperactivity disorder, and dopamine genes

Previous research has suggested that there may be overlap between schizophrenia and attention-deficit hyperactivity disorder (ADHD). The relationship between schizotypal personality traits, ADHD features and polymorphisms was evaluated in dopamine-related genes. Thirty-one healthy, Caucasian men completed the Rust Inventory of Schizotypal Cognitions (RISC) and the ADHD Self-Report Scale (ASRS). Catechol-O-methyltransferase (COMT) Val158Met, dopamine receptors of the D3 type (DRD3) Ser9Gly, DRD4 variable number of tandem repeats (VNTR), and SLC6A3 VNTR polymorphisms were analyzed. RISC score was correlated with ASRS score (r = 0.54, P = 0.003). COMT Met homozygotes had higher ASRS scores than Val homozygotes (P = 0.005). These findings are consistent with evidence of overlap between schizophrenia and ADHD and support an involvement of COMT genotype in ADHD features.     

注意缺陷多动障碍儿童的额叶反应抑制功能研究

目的使用近红外光学成像（fNIRS）技术研究注意缺陷多动障碍（ADHD）儿童的额叶反应抑制功能。方法采用GO-NOGO任务对19例ADHD儿童和14名健康对照进行测试,用CW5的fNIRS系统进行同步扫描。结果对照组在NOGO任务刺激时前额叶氧合血红蛋白浓度增加强于ADHD组（F=2.11,P〈0.01）;而在GO任务刺激时两组间前额叶氧合血红蛋白值变化无明显的差异（F=0.82,P=0.73）。结论 ADHD患儿的反应抑制功能不足,并且与额叶功能低下有关。