Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood

May combine two claims.

Both remitters and persistents had thinner cortex than non-ADHD comparisons, with medium to large effect sizes.

“Both remitters and persistents had thinner cortex than non-ADHD comparisons, with medium to large effect sizes.”

May combine two claims.

After covarying for IQ (in addition to scanner and age), significant cluster centers remained largely unchanged in location, but the clusters were less extensive.

“As shown in eFigure 1 and Author e-Table 6, after covarying for IQ (in addition to scanner and age), significant cluster centers remained largely unchanged in location, but the clusters were less extensive.”

May combine two claims.

Scanned probands had significantly higher rates of alcohol substance use disorder (SUD), non-alcohol SUD, and any SUD than probands who were not scanned.

“However, scanned probands had significantly higher rates of alcohol substance use disorder (SUD), non-alcohol SUD, and any SUD than probands who were not scanned (Author e-Table 3)”

May combine two claims.

Using FDR<0.05, remitters (n=26) did not differ significantly from non-ADHD comparisons; persistents and remitters also did not differ in any region at this threshold.

“Using FDR<0.05, remitters (n=26) did not differ significantly from non-ADHD comparisons; persistents and remitters also did not differ in any region at this threshold.”

May combine two claims.

Cortex was significantly thinner (surface-wide FDR<0.05) in ADHD probands in multiple clusters; the largest cluster extended from right precuneus to precentral gyrus.

“Figure 1A displays the multiple clusters of vertices (detailed in Table 2) for which the cortex was significantly thinner (surface-wide FDR<0.05) in ADHD probands; the largest cluster extended from right precuneus to precentral gyrus.”

May combine two claims.

Average effect sizes between persistents and non-ADHD comparisons (d=0.73) were larger than for remitters (d=0.52), although all confidence intervals overlapped; persistents and remitters did not differ significantly from each other in any cluster at FDR<0.05.

“Average effect sizes between persistents and non-ADHD comparisons (d=0.73) were larger than for remitters (d=0.52), although all confidence intervals overlapped (not shown); persistents and remitters did not differ significantly from each other in any cluster at FDR<0.05 (see Table 2).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Due to refusals and MRI exclusions, we obtained MRI scans in 59 ADHD probands and 80 comparisons.

“Due to refusals and MRI exclusions (see Table 1), we obtained MRI scans in 59 ADHD probands and 80 comparisons.”

May combine two claims.

There were no vertices at which cortical thickness was significantly associated with lifetime or current substance abuse diagnoses, dimensional measures of substance abuse, lifetime smoking history, or thioridazine treatment, nor were there any significant interactions between group and scanner for any cortical or VBM measures.

“There were no vertices at which cortical thickness was significantly associated with lifetime or current substance abuse diagnoses, dimensional measures of substance abuse, lifetime smoking history, or thioridazine treatment, nor were there any significant interactions between group and scanner for any cortical or VBM measures.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Probands and comparisons with current ADHD-NOS did not differ between groups (27% and 29%, respectively).

“probands and comparisons with current ADHD-NOS, which is not well-defined and did not differ between groups (27% and 29%, respectively), were excluded from subgroup analyses.”

May combine two claims.

On average 33 years after initial childhood diagnosis, clinical data were obtained on 135 male probands (65% of original sample, 69% of those living) and 136 male comparisons (76% of 178 recruited in adolescence, 77% of those living).

“On average 33 years after initial childhood diagnosis, clinical data were obtained on 135 male probands (65% of original sample, 69% of those living) and 136 male comparisons (76% of 178 recruited in adolescence, 77% of those living).”

May combine two claims.

Within both proband and comparison groups, individuals scanned and those not scanned did not differ significantly on prevalence of ADHD, Antisocial Personality Disorder, mood or anxiety disorders, any DSM-III disorders, age at referral, IQ, socioeconomic status, or Teacher Conners Hyperactivity Factor score.

“Within both proband and comparison groups, individuals scanned and those not scanned did not differ significantly on prevalence of ADHD, Antisocial Personality Disorder, mood or anxiety disorders, any DSM-III disorders, age at referral, IQ, socioeconomic status, or Teacher Conners Hyperactivity Factor score.”

May combine two claims.

Probands and comparisons did not differ significantly in age at scan, or in lifetime prevalence of substance abuse or dependence.

“Probands and comparisons did not differ significantly in age at scan, or in lifetime prevalence of substance abuse or dependence (see Table 1).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Probands and comparisons differed significantly in IQ in childhood and 41FU assessments.

“As expected, probands and comparisons differed significantly in IQ in childhood and 41FU assessments.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Rates of refusal, failure to schedule or to locate subjects did not differ significantly (45% of probands versus 43% of comparisons).

“By contrast, rates of refusal, failure to schedule or to locate subjects did not differ significantly (45% of probands versus 43% of comparisons).”

May combine two claims.

GM density was significantly greater (FDR<0.05) for comparisons than for probands in many of the same regions identified through cortical thickness analyses as well as in subcortical regions inaccessible to cortex-based measures.

“As shown in Table 3 and Figure 3, GM density was significantly greater (FDR<0.05) for comparisons than for probands in many of the same regions identified through cortical thickness analyses as well as in subcortical regions inaccessible to cortex-based measures.”

May combine two claims.

In the clusters that differentiated persistents from remitters in exploratory vertex-wise analyses, persistents differed markedly from non-ADHD comparisons (average d=0.75), whereas remitters did not (average d=0.03; t(9)=8.26, p<0.0001).

“In the clusters that differentiated persistents from remitters in exploratory vertex-wise analyses, persistents differed markedly from non-ADHD comparisons (average d=0.75), whereas remitters did not (average d=0.03; t(9)=8.26, p<0.0001).”

May combine two claims.

We found similar results in analyses that included all participants as well as in those limited to probands with persistent ADHD versus non-ADHD comparisons.

“We found similar results in analyses that included all participants as well as in those limited to probands with persistent ADHD versus non-ADHD comparisons.”

May combine two claims.

Probands with persistent ADHD differed most from non-ADHD comparisons in the same cortical regions identified in primary analyses, as well as in additional clusters in left medial occipital cortex and subgenual ACC.

“With respect to current adult diagnosis, probands with persistent ADHD differed most from non-ADHD comparisons in the same cortical regions identified in our primary analyses, as well as in additional clusters in left medial occipital cortex and subgenual ACC.”

May combine two claims.

In a prospective 33-year longitudinal follow-up of 59 probands (mean age 41 years) with established ADHD in childhood and 80 prospectively enrolled non-ADHD comparisons, we found an overall significant reduction in mean cortical thickness in probands.

“In a prospective 33-year longitudinal follow-up of 59 probands (mean age 41 years) with established ADHD in childhood and 80 prospectively enrolled non-ADHD comparisons, we found an overall significant reduction in mean cortical thickness in probands.”

May combine two claims.

We did not find group differences in much of prefrontal cortex but found widespread cortical thinning in bilateral parietal-temporal cortex.

“In contrast, we did not find group differences in much of prefrontal cortex but found widespread cortical thinning in bilateral parietal-temporal cortex.”

May combine two claims.

Decreased GM in probands in right caudate, right thalamus and bilateral cerebellar hemispheres.

“Figure 4 displays decreased GM in probands in right caudate, right thalamus and bilateral cerebellar hemispheres.”

May combine two claims.

We found widespread thinner cortex and decreased GM density in bilateral parietal and precentral regions, overlapping areas of the dorsal attentional network.

“First, we found widespread thinner cortex and decreased GM density in bilateral parietal and precentral regions, overlapping areas of the dorsal attentional network.”

May combine two claims.

Our analyses revealed thinner cortex in probands, and particularly those with persistent ADHD, across multiple limbic regions such as temporal poles (BA38), insula (BA13) and subgenual ACC (BA25).

“Second, our analyses revealed thinner cortex in probands, and particularly those with persistent ADHD, across multiple limbic regions such as temporal poles (BA38), insula (BA13) and subgenual ACC (BA25).”

May combine two claims.

Probands had significantly lower IQ than comparisons both in childhood/adolescence and adulthood.

“our probands had significantly lower IQ than comparisons both in childhood/adolescence and adulthood.”

May combine two claims.

In regions in which we found suggestive differences, we observed remarkable congruence between remitters and controls in left superior temporal gyrus, ACC, parahippocampus, and occipital cortical thickness as well as in thalamus and cerebellum gray matter density.

“In regions in which we found suggestive differences, we observed remarkable congruence between remitters and controls in left superior temporal gyrus, ACC, parahippocampus, and occipital cortical thickness as well as in thalamus and cerebellum gray matter density.”

May combine two claims.

We observed thinner cortex in regions subserving both emotional regulation (temporal pole, insula, parahippocampus and subgenual ACC) and top-down attentional regulation (dorsal attentional network and medial occipital cortex).

“We observed thinner cortex in regions subserving both emotional regulation (temporal pole, insula, parahippocampus and subgenual ACC) and top-down attentional regulation (dorsal attentional network and medial occipital cortex).”

May combine two claims.

There were no significant main effects or interactions related to scanner type.

“there were no significant main effects or interactions related to scanner type.”

May combine two claims.

VBM largely echoed these findings and additionally highlighted decreased GM in caudate.

“These findings were largely echoed by VBM, which additionally highlighted decreased GM in caudate.”

Classified as probably not a substantial claim.

Treatment had been discontinued for all subjects for several decades.

“treatment had been discontinued for all subjects for several decades.”

May combine two claims.

Probands with childhood ADHD had thinner overall cortex, and this was even more pronounced in those with persistent ADHD.

“we found thinner overall cortex in probands with childhood ADHD that was even more pronounced in those with persistent ADHD.”

Classified as probably not a substantial claim.

Persistence of ADHD into adulthood is now well documented.

“The diagnosis of ADHD requires onset in childhood, but persistence of ADHD into adulthood is now well documented.4, 5”

• cites [4] Durston S Hulshoff Pol HE Schnack HG Buitelaar JK Steenhuis MP Minderaa RB Kahn RS van Engeland H Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings J Am Acad Child Adolesc Psychiatry 2004 43 3 332 340 15076267Not checked yet

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• cites [5] Kessler RC Adler L Barkley R Biederman J Conners CK Demler O Faraone SV Greenhill LL Howes MJ Secnik K Spencer T Ustun TB Walters EE Zaslavsky AM The prevalence and correlates of adult ADHD in the United States: results from the national comorbidity survey replication Am J Psychiatry 2006 163 4 716 723 16585449 PMC2859678Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

These findings are consistent with a model of ADHD as a disorder of frontal-striatal-cerebellar circuitry.

“These findings are consistent with a model of ADHD as a disorder of frontal-striatal-cerebellar circuitry.”

Classified as probably not a substantial claim. May combine two claims.

Volumetric studies in children with ADHD have consistently found global reductions of total brain volume with prefrontal cortex, anterior and posterior cingulate cortex, basal ganglia, cerebellum and parieto-temporal regions particularly affected relative to typically developing subjects.

“Volumetric studies in children with Attention-Deficit/Hyperactivity Disorder (ADHD) have consistently found global reductions of total brain volume with prefrontal cortex, anterior and posterior cingulate cortex, basal ganglia, cerebellum and parieto-temporal regions particularly affected relative to typically developing subjects.1–4”

• cites [1] Valera EM Faraone SV Murray KE Seidman LJ Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder Biol Psychiatry 2007 61 12 1361 1369 16950217Not checked yet

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• cites [2] Castellanos FX Lee PP Sharp W Jeffries NO Greenstein DK Clasen LS Blumenthal JD James RS Ebens CL Walter JM Zijdenbos A Evans AC Giedd JN Rapoport JL Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder J Am Med Assoc 2002 288 14 1740 1748 12365958Not checked yet

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• cites [3] Krain AL Castellanos FX Brain development and ADHD Clin Psychol Rev 2006 26 4 433 444 16480802Not checked yet

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• cites [4] Durston S Hulshoff Pol HE Schnack HG Buitelaar JK Steenhuis MP Minderaa RB Kahn RS van Engeland H Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings J Am Acad Child Adolesc Psychiatry 2004 43 3 332 340 15076267Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

A sparse literature on brain anatomy in adults with ADHD reports decreased volumes in orbitofrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, superior frontal cortex and cerebellum.

“A sparse literature on brain anatomy in adults with ADHD also reports decreased volumes in orbitofrontal cortex,6 anterior cingulate cortex (ACC),7, 8 dorsolateral prefrontal cortex (DLPFC),9 superior frontal cortex and cerebellum.10”

• cites [6] Hesslinger B Tebartz van Elst L Thiel T Haegele K Hennig J Ebert D Frontoorbital volume reductions in adult patients with attention deficit hyperactivity disorder Neurosci Lett 2002 328 3 319 321 12147334Not checked yet

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• cites [7] Seidman LJ Valera EM Makris N Monuteaux MC Boriel DL Kelkar K Kennedy DN Caviness VS Bush G Aleardi M Faraone SV Biederman J Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging Biol Psychiatry 2006 60 10 1071 1080 16876137Not checked yet

  Not checked in the free run.

• cites [8] Makris N Seidman LJ Valera EM Biederman J Monuteaux MC Kennedy DN Caviness VS Jr Bush G Crum K Brown AB Faraone SV Anterior cingulate volumetric alterations in treatment-naive adults with ADHD: a pilot study J Atten Disord 2010 13 4 407 413 20008822 PMC3746768Not checked yet

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• cites [9] Seidman LJ Valera EM Makris N Monuteaux MC Boriel DL Kelkar K Kennedy DN Caviness VS Bush G Aleardi M Faraone SV Biederman J Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging Biol Psychiatry 2006 60 10 1071 1080 16876137Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Complementary analyses of cortical thickness reveal overall decreased cortical thickness in children and adults with ADHD with reductions in ACC, medial frontal regions and parieto-temporo-occipital cortex.

“Complementary analyses of cortical thickness11 reveal overall decreased cortical thickness in children11–14 and adults with ADHD with reductions in ACC, medial frontal regions and parieto-temporo-occipital cortex.12–14”

• cites [11] Castellanos FX Proal E Location, location, and thickness: volumetric neuroimaging of attention-deficit/hyperactivity disorder comes of age J Am Acad Child Adolesc Psychiatry 2009 48 10 979 981 20854767Not checked yet

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• cites [12] Shaw P Eckstrand K Sharp W Blumenthal J Lerch JP Greenstein D Clasen L Evans A Giedd J Rapoport JL Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation Proc Natl Acad Sci USA 2007 104 49 19649 19654 18024590 PMC2148343Not checked yet

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• cites [13] Narr KL Woods RP Lin J Kim J Phillips OR Del’homme M Caplan R Toga AW McCracken JT Levitt JG Widespread cortical thinning is a robust anatomical marker for attention-deficit/hyperactivity disorder J Am Acad Child Adolesc Psychiatry 2009 48 10 1014 1022 19730275 PMC2891193Not checked yet

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• cites [14] Shaw P Lerch J Greenstein D Sharp W Clasen L Evans A Giedd J Castellanos FX Rapoport J Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder Arch Gen Psychiatry 2006 63 5 540 549 16651511Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Major DSM-IV disorders, as well as multiple aspects of function, were assessed for the interval between 25FU and 41FU by trained clinicians "blind" to all antecedent data.

“Major DSM-IV disorders, as well as multiple aspects of function, were assessed for the interval between 25FU and 41FU by trained clinicians “blind” to all antecedent data.”

Classified as probably not a substantial claim.

For each comparison, we regressed cortical thickness at each of 81,924 vertices or whole-brain GM density on group, controlling for age at time of scan and scanner model.

“For each comparison, we regressed cortical thickness at each of 81,924 vertices or whole-brain GM density on group, controlling for age at time of scan and scanner model.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Exploratory analyses reexamined subgroup differences heuristically using an uncorrected p<0.05 threshold with a cluster threshold of 50 vertices.

“we reexamined subgroup differences heuristically using an uncorrected p<0.05 threshold with a cluster threshold of 50 vertices.47”

• cites [47] Shaw P Sharp WS Morrison M Eckstrand K Greenstein DK Clasen LS Evans AC Rapoport JL Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder Am J Psychiatry 2009 166 1 58 63 18794206 PMC2700349Not checked yet

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Classified as probably not a substantial claim.

Results were thresholded using a false discovery rate (FDR) of 0.05.

“Results were thresholded using a false discovery rate (FDR) of 0.05.45, 46”

• cites [45] Benjamini Y Hochberg Y Controlling the false discovery rate: a practical and powerful approach to multiple testing J R Stat Soc Series B Stat Methodol 1995 57 1 289 300Not checked yet

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• cites [46] Genovese CR Lazar NA Nichols T Thresholding of statistical maps in functional neuroimaging using the false discovery rate Neuroimage 2002 15 4 870 878 11906227Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Proportions did not differ significantly across scanners (χ(1)2=0.96, p=0.33).

“proportions did not differ significantly across scanners, (χ(1)2=0.96, p=0.33)”

Classified as probably not a substantial claim.

Systematic diagnostic assessments at each follow-up were conducted by interviewers "blind" to past history and group membership.

“Systematic diagnostic assessments at each follow-up were conducted by interviewers “blind” to past history and group membership.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Refusal was low (circa 5%).

“Refusal was low (circa 5%).”

Classified as probably not a substantial claim.

ROI-based analyses compared diagnostic subgroups of probands and comparisons without current ADHD, Bonferroni corrected for the number of clusters.

“We then compared the diagnostic subgroups of probands (persistents, remitters) and the comparisons without current ADHD, Bonferroni corrected for the number of clusters.”

Classified as probably not a substantial claim.

We report cortical thickness and VBM analyses on the largest sample to date of adults with childhood ADHD diagnoses consistent with DSM-IV.

“We report cortical thickness and voxel-based morphometry (VBM) analyses on the largest sample to date of adults with childhood ADHD diagnoses (mean age 8) consistent with DSM-IV.”

Classified as probably not a substantial claim. May combine two claims.

Because of significant between-group differences in IQ, we confirmed cortical thickness results by also adjusting for IQ.

“Because of significant between-group differences in IQ, we confirmed cortical thickness results by also adjusting for IQ.”

Classified as probably not a substantial claim.

Linear regression models controlled for age at time of scan and scanner model (Trio vs. Allegra).

“Linear regression models controlled for age at time of scan and scanner model (Trio vs. Allegra).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Almeida et al. found cortical thinning in right frontal lobe of children, adolescents and adults with ADHD.

“Recently, Almeida et al.15 found cortical thinning in right frontal lobe of children, adolescents and adults with ADHD.”

• cites [15] Almeida LG Ricardo-Garcell J Prado H Barajas L Fernandez-Bouzas A Avila D Martinez RB Reduced right frontal cortical thickness in children, adolescents and adults with ADHD and its correlation to clinical variables: A cross-sectional study J Psychiatr Res 2010 44 16 1214 1212 20510424Not checked yet

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Classified as probably not a substantial claim.

Medical center pediatric charts were reviewed for children seen for routine physical exams from 1970-1977 when they were 6 through 12 years-old, group-matched for probands' race, childhood socioeconomic status and geographical residence.

“Medical center pediatric charts were reviewed for children seen for routine physical exams from 1970–1977 when they were 6 through 12 years-old, group-matched for probands’ race, childhood socioeconomic status and geographical residence.”

Classified as probably not a substantial claim. May combine two claims.

We retained clusters comprising at least 50 contiguous vertices for cortical thickness and five voxels for VBM.

“We retained clusters comprising at least 50 contiguous vertices for cortical thickness47 and five voxels for VBM.”

• cites [47] Shaw P Sharp WS Morrison M Eckstrand K Greenstein DK Clasen LS Evans AC Rapoport JL Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder Am J Psychiatry 2009 166 1 58 63 18794206 PMC2700349Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

A cross-sectional study of children, adolescents and adults found that individuals with ADHD, regardless of age, had significantly thinner right superior frontal cortex than controls.

“A cross-sectional study of children, adolescents and adults found that individuals with ADHD, regardless of age, had significantly thinner right superior frontal cortex than controls.15”

• cites [15] Almeida LG Ricardo-Garcell J Prado H Barajas L Fernandez-Bouzas A Avila D Martinez RB Reduced right frontal cortical thickness in children, adolescents and adults with ADHD and its correlation to clinical variables: A cross-sectional study J Psychiatr Res 2010 44 16 1214 1212 20510424Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Thinner cortex has been reported in children with ADHD in prefrontal and precentral regions, parietal and temporal lobes and inferior frontal gyrus bilaterally.

“Thinner cortex has been reported in children with ADHD in prefrontal and precentral regions12, 14 parietal and temporal lobes12, 13 and inferior frontal gyrus bilaterally.58”

• cites [12] Shaw P Eckstrand K Sharp W Blumenthal J Lerch JP Greenstein D Clasen L Evans A Giedd J Rapoport JL Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation Proc Natl Acad Sci USA 2007 104 49 19649 19654 18024590 PMC2148343Not checked yet

  Not checked in the free run.

• cites [14] Shaw P Lerch J Greenstein D Sharp W Clasen L Evans A Giedd J Castellanos FX Rapoport J Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder Arch Gen Psychiatry 2006 63 5 540 549 16651511Not checked yet

  Not checked in the free run.

• cites [13] Narr KL Woods RP Lin J Kim J Phillips OR Del’homme M Caplan R Toga AW McCracken JT Levitt JG Widespread cortical thinning is a robust anatomical marker for attention-deficit/hyperactivity disorder J Am Acad Child Adolesc Psychiatry 2009 48 10 1014 1022 19730275 PMC2891193Not checked yet

  Not checked in the free run.

• cites [58] Batty MJ Liddle EB Pitiot A Toro R Groom MJ Scerif G Liotti M Liddle PF Paus T Hollis C Cortical gray matter in attention-deficit/hyperactivity disorder: a structural magnetic resonance imaging study J Am Acad Child Adolesc Psychiatry 49 3 229 238 20410712 PMC2829134Not checked yet

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Classified as probably not a substantial claim.

Our results extend prior volumetric and cortical thickness findings in ADHD.

“Our results extend prior volumetric and cortical thickness findings in ADHD.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the adults with ADHD, the specific reduction, with correction for multiple comparisons limited to the frontal lobe, was localized to BA9.

“In the adults with ADHD, the specific reduction, with correction for multiple comparisons limited to the frontal lobe, was localized to BA9.”

• cites [15] Almeida LG Ricardo-Garcell J Prado H Barajas L Fernandez-Bouzas A Avila D Martinez RB Reduced right frontal cortical thickness in children, adolescents and adults with ADHD and its correlation to clinical variables: A cross-sectional study J Psychiatr Res 2010 44 16 1214 1212 20510424Not checked yet

  Not checked in the free run.

May combine two claims.

In our main analyses, we applied FDR full-brain correction for multiple comparisons, and observed significant differences whether groups were defined by initial childhood history or by current adult diagnoses.

“In our main analyses, we applied FDR full-brain correction for multiple comparisons, and observed significant differences whether groups were defined by initial childhood history or by current adult diagnoses.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Studies of cortical thickness in children with ADHD are more numerous than those in adults, and typically have examined the entire cerebrum, although nearly all (except14) report results uncorrected for multiple comparisons.

“Studies of cortical thickness in children with ADHD are more numerous than those in adults,12–14, 33, 47, 56, 57 and typically have examined the entire cerebrum, although nearly all (except14) report results uncorrected for multiple comparisons.”

• cites [12] Shaw P Eckstrand K Sharp W Blumenthal J Lerch JP Greenstein D Clasen L Evans A Giedd J Rapoport JL Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation Proc Natl Acad Sci USA 2007 104 49 19649 19654 18024590 PMC2148343Not checked yet

  Not checked in the free run.

• cites [13] Narr KL Woods RP Lin J Kim J Phillips OR Del’homme M Caplan R Toga AW McCracken JT Levitt JG Widespread cortical thinning is a robust anatomical marker for attention-deficit/hyperactivity disorder J Am Acad Child Adolesc Psychiatry 2009 48 10 1014 1022 19730275 PMC2891193Not checked yet

  Not checked in the free run.

• cites [14] Shaw P Lerch J Greenstein D Sharp W Clasen L Evans A Giedd J Castellanos FX Rapoport J Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder Arch Gen Psychiatry 2006 63 5 540 549 16651511Not checked yet

  Not checked in the free run.

• cites [33] Shaw P Gornick M Lerch J Addington A Seal J Greenstein D Sharp W Evans A Giedd JN Castellanos FX Rapoport JL Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder Arch Gen Psychiatry 2007 64 8 921 931 17679637Not checked yet

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• cites [47] Shaw P Sharp WS Morrison M Eckstrand K Greenstein DK Clasen LS Evans AC Rapoport JL Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder Am J Psychiatry 2009 166 1 58 63 18794206 PMC2700349Not checked yet

  Not checked in the free run.

• cites [56] Shaw P Lalonde F Lepage C Rabin C Eckstrand K Sharp W Greenstein D Evans A Giedd JN Rapoport J Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder Arch Gen Psychiatry 2009 66 8 888 896 19652128 PMC2948210Not checked yet

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• cites [57] Wolosin SM Richardson ME Hennessey JG Denckla MB Mostofsky SH Abnormal cerebral cortex structure in children with ADHD Hum Brain Mapp 2009 30 1 175 184 17985349 PMC2883170Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Studies of cortical thickness in adults with ADHD have focused on specific regions associated with executive function and attentional control.

“Studies of cortical thickness in adults with ADHD have focused on specific regions associated with executive function and attentional control.54, 55”

• cites [54] Posner MI Petersen SE The attention system of the human brain Annu Rev Neurosci 1990 13 25 42 2183676Not checked yet

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• cites [55] Corbetta M Shulman GL Control of goal-directed and stimulus-driven attention in the brain Nat Rev Neurosci 2002 3 3 201 215 11994752Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Makris et al. selected nine parcellation units (from 48) per hemisphere and found thinner cortex related to ADHD in prefrontal and cingulate cortex and inferior parietal lobe, albeit without correcting for multiple comparisons.

“Makris et al.9 selected nine parcellation units (from 48) per hemisphere and found thinner cortex related to ADHD in prefrontal and cingulate cortex and inferior parietal lobe, albeit without correcting for multiple comparisons.9”

• cites [9] Seidman LJ Valera EM Makris N Monuteaux MC Boriel DL Kelkar K Kennedy DN Caviness VS Bush G Aleardi M Faraone SV Biederman J Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging Biol Psychiatry 2006 60 10 1071 1080 16876137Not checked yet

  Not checked in the free run.

May combine two claims.

We found less frontal and prefrontal cortical thinning in ADHD than others, but confirmed thinner cortical mantle in occipito-parietal, temporal cortex and precentral regions in ADHD.

“Furthermore, although we found less frontal and prefrontal cortical thinning in ADHD than others,12–15, 20, 49 we confirmed thinner cortical mantle in occipito-parietal,12, 13, 20 temporal cortex and precentral regions13, 14 in ADHD.”

• cites [12] Shaw P Eckstrand K Sharp W Blumenthal J Lerch JP Greenstein D Clasen L Evans A Giedd J Rapoport JL Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation Proc Natl Acad Sci USA 2007 104 49 19649 19654 18024590 PMC2148343Not checked yet

  Not checked in the free run.

• cites [13] Narr KL Woods RP Lin J Kim J Phillips OR Del’homme M Caplan R Toga AW McCracken JT Levitt JG Widespread cortical thinning is a robust anatomical marker for attention-deficit/hyperactivity disorder J Am Acad Child Adolesc Psychiatry 2009 48 10 1014 1022 19730275 PMC2891193Not checked yet

  Not checked in the free run.

• cites [14] Shaw P Lerch J Greenstein D Sharp W Clasen L Evans A Giedd J Castellanos FX Rapoport J Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder Arch Gen Psychiatry 2006 63 5 540 549 16651511Not checked yet

  Not checked in the free run.

• cites [15] Almeida LG Ricardo-Garcell J Prado H Barajas L Fernandez-Bouzas A Avila D Martinez RB Reduced right frontal cortical thickness in children, adolescents and adults with ADHD and its correlation to clinical variables: A cross-sectional study J Psychiatr Res 2010 44 16 1214 1212 20510424Not checked yet

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• cites [20] Makris N Biederman J Valera EM Bush G Kaiser J Kennedy DN Caviness VS Faraone SV Seidman LJ Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder Cereb Cortex 2007 17 6 1364 1375 16920883Not checked yet

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• cites [49] Sowell ER Thompson PM Welcome SE Henkenius AL Toga AW Peterson BS Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder The Lancet 2003 362 9397 1699 1707 14643117Not checked yet

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May combine two claims.

We found convincing converging anatomic evidence implicating the dorsal attentional network and distributed regions within limbic circuits that were thinner in ADHD probands than in comparisons.

“We found convincing converging anatomic evidence implicating the dorsal attentional network55 and distributed regions within limbic circuits that were thinner in ADHD probands than in comparisons.”

• cites [55] Corbetta M Shulman GL Control of goal-directed and stimulus-driven attention in the brain Nat Rev Neurosci 2002 3 3 201 215 11994752Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The bilateral dorsal network mediates goal-directed, top-down executive control processes, interacts with a right-sided ventral system during attentional functioning, particularly in redirecting attention.

“The bilateral dorsal network, which mediates goal-directed, top-down executive control processes, interacts with a right-sided ventral system (stimulus-driven, bottom-up) during attentional functioning,1, 55 particularly in redirecting attention.”

• cites [1] Valera EM Faraone SV Murray KE Seidman LJ Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder Biol Psychiatry 2007 61 12 1361 1369 16950217Not checked yet

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• cites [55] Corbetta M Shulman GL Control of goal-directed and stimulus-driven attention in the brain Nat Rev Neurosci 2002 3 3 201 215 11994752Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Early anatomical studies of ADHD did not specifically examine thalamic nuclei, although thalamic hypoactivation emerged in an unbiased meta-analysis.

“Early anatomical studies of ADHD did not specifically examine thalamic nuclei, although thalamic hypoactivation emerged in an unbiased meta-analysis.52”

• cites [52] Dickstein SG Bannon K Castellanos FX Milham MP The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis J Child Psychol Psychiatry 2006 47 10 1051 1062 17073984Not checked yet

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Classified as probably not a substantial claim.

The core areas constituting the dorsal attentional network include the intraparietal sulcus and the conjunction of the precentral and superior frontal sulcus (frontal eye fields).

“The core areas constituting the dorsal attentional network include the intraparietal sulcus and the conjunction of the precentral and superior frontal sulcus (frontal eye fields)55 which were particularly affected in the ADHD probands.”

• cites [55] Corbetta M Shulman GL Control of goal-directed and stimulus-driven attention in the brain Nat Rev Neurosci 2002 3 3 201 215 11994752Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Individuals with ADHD are easily distracted when required to ignore extraneous signals.

“Individuals with ADHD are easily distracted when required to ignore extraneous signals.70, 71”

• cites [70] Lijffijt M Kenemans JL Verbaten MN van Engeland H A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: deficient inhibitory motor control? J Abnorm Psychol 2005 114 2 216 222 15869352Not checked yet

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• cites [71] Clark L Blackwell AD Aron AR Turner DC Dowson J Robbins TW Sahakian BJ Association between response inhibition and working memory in adult ADHD: a link to right frontal cortex pathology? Biol Psychiatry 2007 61 12 1395 1401 17046725Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Top-down control deficits when responding to irrelevant stimuli are associated with impaired working memory.

“Top-down control deficits when responding to irrelevant stimuli are associated with impaired working memory.72, 73”

• cites [72] Zanto TP Rubens MT Bollinger J Gazzaley A Top-down modulation of visual feature processing: The role of the inferior frontal junction Neuroimage 2010 53 2 736 745 20600999 PMC2930130Not checked yet

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• cites [73] Gazzaley A D’Esposito M Top-down modulation and normal aging Ann N Y Acad Sci 2007 1097 67 83 17413013Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Abnormal activation of occipital cortex has been found in youth and adults with ADHD during working memory tasks.

“Abnormal activation of occipital cortex has been found in youth74 and adults75–77 with ADHD during working memory tasks.”

• cites [74] Durston S Tottenham NT Thomas KM Davidson MC Eigsti IM Yang Y Ulug AM Casey BJ Differential patterns of striatal activation in young children with and without ADHD Biol Psychiatry 2003 53 10 871 878 12742674Not checked yet

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• cites [75] Schweitzer JB Faber TL Grafton ST Tune LE Hoffman JM Kilts CD Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder Am J Psychiatry 2000 157 2 278 280 10671402Not checked yet

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• cites [76] Schweitzer JB Lee DO Hanford RB Tagamets MA Hoffman JM Grafton ST Kilts CD A positron emission tomography study of methylphenidate in adults with ADHD: alterations in resting blood flow and predicting treatment response Neuropsychopharmacology 2003 28 5 967 973 12700698Not checked yet

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• cites [77] Schweitzer JB Hanford RB Medoff DR Working memory deficits in adults with ADHD: is there evidence for subtype differences? Behav Brain Funct 2006 2 43 17173676 PMC1762010Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Cerebellar involvement in ADHD is well-established, with findings in children reported mostly in the vermis, and in the hemispheres in adults, as in this sample.

“Cerebellar involvement in ADHD is well-established, with findings in children reported mostly in the vermis,1–4, 79 and in the hemispheres in adults, as in this sample.60, 80, 81”

• cites [1] Valera EM Faraone SV Murray KE Seidman LJ Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder Biol Psychiatry 2007 61 12 1361 1369 16950217Not checked yet

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• cites [2] Castellanos FX Lee PP Sharp W Jeffries NO Greenstein DK Clasen LS Blumenthal JD James RS Ebens CL Walter JM Zijdenbos A Evans AC Giedd JN Rapoport JL Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder J Am Med Assoc 2002 288 14 1740 1748 12365958Not checked yet

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• cites [3] Krain AL Castellanos FX Brain development and ADHD Clin Psychol Rev 2006 26 4 433 444 16480802Not checked yet

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• cites [4] Durston S Hulshoff Pol HE Schnack HG Buitelaar JK Steenhuis MP Minderaa RB Kahn RS van Engeland H Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings J Am Acad Child Adolesc Psychiatry 2004 43 3 332 340 15076267Not checked yet

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• cites [79] Castellanos FX Giedd JN Berquin PC Walter JM Sharp W Tran T Vaituzis AC Blumenthal JD Nelson J Bastain TM Zijdenbos A Evans AC Rapoport JL Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder Arch Gen Psychiatry 2001 58 3 289 295 11231836Not checked yet

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• cites [60] Wolf RC Plichta MM Sambataro F Fallgatter AJ Jacob C Lesch KP Herrmann MJ Schonfeldt-Lecuona C Connemann BJ Gron G Vasic N Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention-deficit/hyperactivity disorder Hum Brain Mapp 2009 30 7 2252 2266 19107748 PMC6870879Not checked yet

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• cites [80] Perlov E Tebarzt van Elst L Buechert M Maier S Matthies S Ebert D Hesslinger B Philipsen A H(1)-MR-spectroscopy of cerebellum in adult attention deficit/hyperactivity disorder J Psychiatr Res 2010 44 14 938 943 20332052Not checked yet

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• cites [81] Valera EM Spencer RM Zeffiro TA Makris N Spencer TJ Faraone SV Biederman J Seidman LJ Neural substrates of impaired sensorimotor timing in adult attention-deficit/hyperactivity disorder Biol Psychiatry 2010 68 4 359 367 20619827 PMC2917236Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The insula and ACC play important roles in sensorimotor, emotional and cognitive function.

“The insula and ACC play important roles in sensorimotor, emotional and cognitive function.85, 86”

• cites [85] Pollatos O Gramann K Schandry R Neural systems connecting interoceptive awareness and feelings Hum Brain Mapp 2007 28 1 9 18 16729289 PMC6871500Not checked yet

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• cites [86] Craig AD How do you feel? Interoception: the sense of the physiological condition of the body Nat Rev Neurosci 2002 3 8 655 666 12154366Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

In a meta-analysis of functional imaging studies, children and adolescents with ADHD showed activation decreases in left middle occipital gyrus (BA19) compared to controls.

“Similarly, in a meta-analysis of functional imaging studies, children and adolescents with ADHD showed activation decreases in left middle occipital gyrus (BA19) compared to controls.52”

• cites [52] Dickstein SG Bannon K Castellanos FX Milham MP The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis J Child Psychol Psychiatry 2006 47 10 1051 1062 17073984Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

These findings are consistent with studies of ADHD that report abnormal patterns of activation in parietal regions during working memory, attentional or response inhibition tasks.

“These findings are consistent with studies of ADHD that report abnormal patterns of activation in parietal regions52 during working memory,60–62 attentional63–65 or response inhibition tasks.66, 67”

• cites [52] Dickstein SG Bannon K Castellanos FX Milham MP The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis J Child Psychol Psychiatry 2006 47 10 1051 1062 17073984Not checked yet

  Not checked in the free run.

• cites [60] Wolf RC Plichta MM Sambataro F Fallgatter AJ Jacob C Lesch KP Herrmann MJ Schonfeldt-Lecuona C Connemann BJ Gron G Vasic N Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention-deficit/hyperactivity disorder Hum Brain Mapp 2009 30 7 2252 2266 19107748 PMC6870879Not checked yet

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• cites [61] Bayerl M Dielentheis TF Vucurevic G Gesierich T Vogel F Fehr C Stoeter P Huss M Konrad A Disturbed brain activation during a working memory task in drug-naive adult patients with ADHD Neuroreport 2010 21 6 442 446 20224456Not checked yet

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• cites [62] Burgess GC Depue BE Ruzic L Willcutt EG Du YP Banich MT Attentional control activation relates to working memory in attention-deficit/hyperactivity disorder Biol Psychiatry 2010 67 7 632 640 20060961 PMC2953472Not checked yet

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• cites [63] Banich MT Burgess GC Depue BE Ruzic L Bidwell LC Hitt-Laustsen S Du YP Willcutt EG The neural basis of sustained and transient attentional control in young adults with ADHD Neuropsychologia 2009 47 14 3095 3104 19619566 PMC3703501Not checked yet

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• cites [64] Cubillo A Halari R Ecker C Giampietro V Taylor E Rubia K Reduced activation and inter-regional functional connectivity of fronto-striatal networks in adults with childhood Attention-Deficit Hyperactivity Disorder (ADHD) and persisting symptoms during tasks of motor inhibition and cognitive switching J Psychiatr Res 2010 44 10 629 639 20060129Not checked yet

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• cites [65] Schneider MF Krick CM Retz W Hengesch G Retz-Junginger P Reith W Rosler M Impairment of fronto-striatal and parietal cerebral networks correlates with attention deficit hyperactivity disorder (ADHD) psychopathology in adults - a functional magnetic resonance imaging (fMRI) study Psychiatry Res 2010 183 1 75 84 20558047Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Recently, several studies have identified thalamic abnormalities in children/adolescents and adults with ADHD.

“Recently, several studies have identified thalamic abnormalities in children/adolescents53, 82 and adults with ADHD.83, 84”

• cites [53] Ivanov I Bansal R Hao X Zhu H Kellendonk C Miller L Sanchez-Pena J Miller AM Chakravarty MM Klahr K Durkin K Greenhill LL Peterson BS Morphological abnormalities of the thalamus in youths with attention deficit hyperactivity disorder Am J Psychiatry 2010 167 4 397 408 20123910 PMC4282161Not checked yet

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• cites [82] Qiu MG Ye Z Li QY Liu GJ Xie B Wang J Changes of brain structure and function in ADHD children Brain Topogr 2010 ePub Dec 30 2010 21191807Not checked yet

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• cites [83] Cubillo A Halari R Ecker C Giampietro V Taylor E Rubia K Reduced activation and inter-regional functional connectivity of fronto-striatal networks in adults with childhood Attention-Deficit Hyperactivity Disorder (ADHD) and persisting symptoms during tasks of motor inhibition and cognitive switching J Psychiatr Res 2010 44 10 629 639 20060129Not checked yet

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• cites [84] Dibbets P Evers EA Hurks PP Bakker K Jolles J Differential brain activation patterns in adult attention-deficit hyperactivity disorder (ADHD) associated with task switching Neuropsychology 2010 24 4 413 423 20604616Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

A recent VBM study in adults with ADHD found significant bilateral reduction of GM volume only in early visual cortex.

“Additionally, a recent VBM study in adults with ADHD found significant bilateral reduction of GM volume only in early visual cortex.78”

• cites [78] Ahrendts J Rusch N Wilke M Philipsen A Eickhoff SB Glauche V Perlov E Ebert D Hennig J Tebartz van Elst L Visual cortex abnormalities in adults with ADHD: A structural MRI study World J Biol Psychiatry ePub Sep 29 2010 20879808Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Occipital cortex has been recently found to interact with the dorsal network in maintaining attention and in suppressing responses to irrelevant stimuli.

“Occipital cortex has been recently found to interact with the dorsal network in maintaining attention59 and in suppressing responses to irrelevant stimuli.68, 69”

• cites [59] Shulman GL Astafiev SV Franke D Pope DL Snyder AZ McAvoy MP Corbetta M Interaction of stimulus-driven reorienting and expectation in ventral and dorsal frontoparietal and basal ganglia-cortical networks J Neurosci 2009 29 14 4392 4407 19357267 PMC2743562Not checked yet

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• cites [68] Capotosto P Babiloni C Romani GL Corbetta M Frontoparietal cortex controls spatial attention through modulation of anticipatory alpha rhythms J Neurosci 2009 29 18 5863 5872 19420253 PMC2692025Not checked yet

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• cites [69] Mevorach C Hodsoll J Allen H Shalev L Humphreys G Ignoring the elephant in the room: a neural circuit to downregulate salience J Neurosci 2010 30 17 6072 6079 20427665 PMC6632594Not checked yet

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May combine two claims.

The probands studied did not differ significantly from those excluded on nearly all clinical and demographic variables, except for significantly higher rates of substance use disorders at 18FU in scanned probands.

“the probands studied did not differ significantly from those excluded on nearly all clinical and demographic variables, except for significantly higher rates of substance use disorders at 18FU in scanned probands.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The insula, along with participating in performance of demanding tasks, is clearly also related to affective processing.

“In turn, the insula, along with participating in performance of demanding tasks,90 is clearly also related to affective processing.91”

• cites [90] Eckert MA Menon V Walczak A Ahlstrom J Denslow S Horwitz A Dubno JR At the heart of the ventral attention system: the right anterior insula Hum Brain Mapp 2009 30 8 2530 2541 19072895 PMC2712290Not checked yet

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• cites [91] Quartz SR Reason, emotion and decision-making: risk and reward computation with feeling Trends Cogn Sci 2009 13 5 209 215 19362037Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Anatomic "spiraling" circuits begin with emotion/motivation pathways which influence "cool" cognitive processes, which in turn control motor responses.

“Anatomic “spiraling” circuits begin with emotion/motivation pathways which influence “cool” cognitive processes, which in turn control motor responses.106”

• cites [106] Haber SN The primate basal ganglia: parallel and integrative networks J Chem Neuroanat 2003 26 4 317 330 14729134Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The temporal poles have been proposed as a channel for the integration of emotion and perception, playing an important role in both emotional and social functions.

“The temporal poles have been proposed as a channel for the integration of emotion and perception, playing an important role in both emotional and social functions.92”

• cites [92] Olson IR Plotzker A Ezzyat Y The enigmatic temporal pole: a review of findings on social and emotional processing Brain 2007 130 Pt 7 1718 1731 17392317Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Subgenual ACC is implicated in emotional processing and pain perception.

“Specifically, subgenual ACC is implicated in emotional processing and pain perception.87”

• cites [87] Vogt BA Vogt L Farber NB Bush G Architecture and neurocytology of monkey cingulate gyrus J Comp Neurol 2005 485 3 218 239 15791645 PMC2649765Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Cortical thickness studies in ADHD have downplayed findings in the temporal pole, which have been reported but not discussed.

“Cortical thickness studies in ADHD have downplayed findings in the temporal pole, which have been reported but not discussed.12–14”

• cites [12] Shaw P Eckstrand K Sharp W Blumenthal J Lerch JP Greenstein D Clasen L Evans A Giedd J Rapoport JL Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation Proc Natl Acad Sci USA 2007 104 49 19649 19654 18024590 PMC2148343Not checked yet

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• cites [13] Narr KL Woods RP Lin J Kim J Phillips OR Del’homme M Caplan R Toga AW McCracken JT Levitt JG Widespread cortical thinning is a robust anatomical marker for attention-deficit/hyperactivity disorder J Am Acad Child Adolesc Psychiatry 2009 48 10 1014 1022 19730275 PMC2891193Not checked yet

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• cites [14] Shaw P Lerch J Greenstein D Sharp W Clasen L Evans A Giedd J Castellanos FX Rapoport J Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder Arch Gen Psychiatry 2006 63 5 540 549 16651511Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The temporal pole (BA38) is classified as a paralimbic region, based on its interconnections with both amygdala and orbitofrontal cortex, and is implicated in social and emotional processes.

“The temporal pole (BA38) is classified as a paralimbic region, based on its interconnections with both amygdala and orbitofrontal cortex, and is implicated in social and emotional processes.92”

• cites [92] Olson IR Plotzker A Ezzyat Y The enigmatic temporal pole: a review of findings on social and emotional processing Brain 2007 130 Pt 7 1718 1731 17392317Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Altered activation in temporal pole is associated with deficits in face recognition and mentalizing.

“Altered activation in temporal pole is associated with deficits in face recognition93–100 and mentalizing, i.e., theory of mind.101–104”

• cites [93] Mackay CE Roberts N Mayes AR Downes JJ Foster JK Mann D An exploratory study of the relationship between face recognition memory and the volume of medial temporal lobe structures in healthy young males Behav Neurol 1998 11 1 3 20 11568398Not checked yet

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• cites [94] Nakamura K Kawashima R Sato N Nakamura A Sugiura M Kato T Hatano K Ito K Fukuda H Schormann T Zilles K Functional delineation of the human occipito-temporal areas related to face and scene processing. A PET study Brain 2000 123 Pt 9 1903 1912 10960054Not checked yet

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• cites [95] Grabowski TJ Damasio H Tranel D Ponto LL Hichwa RD Damasio AR A role for left temporal pole in the retrieval of words for unique entities Hum Brain Mapp 2001 13 4 199 212 11410949 PMC6871982Not checked yet

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• cites [96] Dupont S Investigating temporal pole function by functional imaging Epileptic Disord 2002 4 Suppl 1 S17 22 12424086Not checked yet

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• cites [97] Nelson EE McClure EB Monk CS Zarahn E Leibenluft E Pine DS Ernst M Developmental differences in neuronal engagement during implicit encoding of emotional faces: an event-related fMRI study J Child Psychol Psychiatry 2003 44 7 1015 1024 14531584Not checked yet

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• cites [98] Tsukiura T Namiki M Fujii T Iijima T Time-dependent neural activations related to recognition of people’s names in emotional and neutral face-name associative learning: an fMRI study Neuroimage 2003 20 2 784 794 14568451Not checked yet

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• cites [99] Griffith HR Richardson E Pyzalski RW Bell B Dow C Hermann BP Seidenberg M Memory for famous faces and the temporal pole: functional imaging findings in temporal lobe epilepsy Epilepsy Behav 2006 9 1 173 180 16766230Not checked yet

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• cites [100] Kim JW Kim JJ Jeong BS Ki SW Im DM Lee SJ Lee HS Neural mechanism for judging the appropriateness of facial affect Brain Res Cogn Brain Res 2005 25 3 659 667 16226433Not checked yet

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• cites [101] Jimura K Konishi S Asari T Miyashita Y Temporal pole activity during understanding other persons’ mental states correlates with neuroticism trait Brain Res 2010 1328 104 112 20226769Not checked yet

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• cites [102] Mier D Lis S Neuthe K Sauer C Esslinger C Gallhofer B Kirsch P The involvement of emotion recognition in affective theory of mind Psychophysiology 2010 47 6 1028 1039 20456660Not checked yet

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May combine two claims.

Imaging data were analyzed from only 28% of initially diagnosed probands with ADHD and 45% of comparison subjects.

“We were able to analyze imaging data from only 28% of initially diagnosed probands with ADHD and 45% of comparison subjects.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In humans, subgenual ACC is functionally connected with multiple limbic regions including temporal poles and insula.

“In humans, subgenual ACC is functionally connected with multiple limbic regions including temporal poles88 and insula.89”

• cites [88] Margulies DS Kelly AM Uddin LQ Biswal BB Castellanos FX Milham MP Mapping the functional connectivity of anterior cingulate cortex Neuroimage 2007 37 2 579 588 17604651Not checked yet

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• cites [89] Taylor KS Seminowicz DA Davis KD Two systems of resting state connectivity between the insula and cingulate cortex Hum Brain Mapp 2009 30 9 2731 2745 19072897 PMC6871122Not checked yet

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Classified as probably not a substantial claim.

Exclusion of conduct disorder comorbidity in childhood averted confusion as to the origin of the deficits found in cortical thickness or GM density.

“Exclusion of conduct disorder comorbidity (see Author e-Text) in childhood also averted confusion as to the origin of the deficits found in cortical thickness or GM density.”

May combine two claims.

The results may not generalize to ADHD in women or to other racial or ethnic groups.

“Thus our results may not generalize to ADHD in women or to other racial or ethnic groups.”

May combine two claims.

Our data suggest superior temporal, medial occipital and thalamo-cerebellar involvement in remission.

“While we found supporting evidence for ACC and orbitofrontal involvement in diagnostic remission of ADHD, our data also suggest superior temporal, medial occipital and thalamo-cerebellar involvement in remission.”

Classified as probably not a substantial claim.

The constraint of limiting subjects to Caucasian males avoided potential confounds from possible sex, ethnic, or socioeconomic differences.

“However, this constraint avoided potential confounds from possible sex, ethnic, or socioeconomic differences.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Abnormal activations in insula and subgenual ACC were reported in a meta-analysis of ADHD functional imaging.

“Abnormal activations in insula and subgenual ACC were reported in a meta-analysis of ADHD functional imaging.52”

• cites [52] Dickstein SG Bannon K Castellanos FX Milham MP The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis J Child Psychol Psychiatry 2006 47 10 1051 1062 17073984Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Medication treatment has been reported to affect cortical thickness.

“Medication treatment has been reported to affect cortical thickness47”

• cites [47] Shaw P Sharp WS Morrison M Eckstrand K Greenstein DK Clasen LS Evans AC Rapoport JL Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder Am J Psychiatry 2009 166 1 58 63 18794206 PMC2700349Not checked yet

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Probably not a substantial claim: may not pass S4 (based).

This is the first study of childhood ADHD prospectively examined in adulthood.

“in this first study of childhood ADHD prospectively examined in adulthood”