Revisiting the role of the prefrontal cortex in the pathophysiology of attention-deficit/hyperactivity disorder.
Abstract
Most neural models for the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) have centered on the prefrontal cortex and its interconnections with the striatum and other subcortical structures. However, research only partially supports these models, and they do not correspond with the development of the prefrontal cortex and its interrelated neurocircuitry. The neural and functional development of the prefrontal cortex more closely parallels recovery from ADHD as indicated by the developmental remission of symptomatology. The authors hypothesize that ADHD is due to noncortical dysfunction that manifests early in ontogeny, remains static throughout the lifetime, and is not associated with the remission of symptomatology. Data supporting this neurodevelopmental model of prefrontal cortex function in ADHD are reviewed. Research and treatment implications are discussed.
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They hypothesized that ADHD is caused by non-cortical neural dysfunction that is present early in ontogeny and remains relatively static throughout life.
“they hypothesized that ADHD is caused by non-cortical neural dysfunction that is present early in ontogeny and remains relatively static throughout life.”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Halperin et al., 2006
Halperin and colleagues have posited distinct neurocognitive mechanisms for the etiology of and relative recovery from ADHD.
“Halperin and colleagues (Halperin et al., 2006; Halperin, Marks, & Schulz, 2008) have posited distinct neurocognitive mechanisms for the etiology of and relative recovery from ADHD.”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Halperin et al., 2006
Investigators increasingly embrace the notion that ADHD is best viewed within the context of a developmental trajectory rather than as a static medical condition.
“investigators have increasingly embraced the notion that ADHD is best viewed within the context of a developmental trajectory rather than that of a static medical condition (Halperin et al., 2006; Sagvolden, Johansen, Aase, & Russell, 2005; Sonuga-Barke & Halperin, 2009; Taylor, 1999)”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Halperin et al., 2006
They posited that the reduction of symptoms often seen over development is at least partially accounted for by the degree to which prefrontally-mediated EFs and other higher cortical functions can compensate for primary and enduring subcortical deficits.
“they posited that the reduction of symptoms oftentimes seen over development are at least partially accounted for by the degree to which prefrontally-mediated EFs and other higher cortical functions, which emerge throughout childhood and adolescence, can compensate for these more primary and enduring subcortical deficits.”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Halperin et al., 2006
Many children with ADHD have difficulties with EFs; improved EF over development should reduce severity of ADHD symptoms and impairments.
“This intervention is relevant to ADHD given the noted difficulties that many children with ADHD have with EFs (Doyle, 2006; Willcutt et al., 2005) and the notion that improved EF over development should reduce the severity of ADHD symptoms and impairments (Halperin and Schulz, 2006).”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Halperin and Schulz, 2006
The prefrontal recovery hypothesis postulates that the reduction of ADHD symptoms during adolescence is related to the degree in which prefrontal cognitive control functions ('cold' decision-making) compensate for primary and persistent subcortical deficits ('hot' decision-making).
“The prefrontal recovery hypothesis [73] postulates that the reduction of ADHD symptoms during adolescence is related to the degree in which prefrontal cognitive control functions (‘cold’ decision-making) compensate for primary and persistent subcortical deficits (‘hot’ decision-making).”
From Risky behavior in gambling tasks in individuals with ADHD–a systematic literature review (2013) · cites this paper as [73]
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“One potential mechanism is suggested by the developmental hypothesis of Jeffrey Halperin, which proposed that ADHD is linked to an early-appearing and enduring subcortical dysfunction (weak arousal mechanisms), while symptom remission is dependent on the extent of maturational changes in executive control [61,62].”
Hoogman, M., Bralten, J., Hibar, D. P., Mennes, M., Zwiers, M. P., Schweren, L. S. J., van Hulzen, K. J. E., Medland, S. E., Shumskaya, E., Jahanshad, N., et al. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30049-4 · Cited by 879 · see citing works
Hart, H., Radua, J., Nakao, T., Mataix-Cols, D., & Rubia, K. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.277 · Cited by 764 · see citing works
“Together, these data suggest that basal ganglia deficits may normalize in ADHD adulthood, while frontal deficits may become more prominent, in line with theories that suggest that frontal lobe deficits in ADHD may be secondary to primary subcortical deficits.(110) Overall, the findings illustrate that age, long-term s…”
BackgroundReaction time variability in ADHD: A meta-analytic review of 319 studies
Kofler, M. J., Rapport, M. D., Sarver, D. E., Raiker, J. S., Orban, S. A., Friedman, L. M., & Kolomeyer, E. G. (2013) · Clinical Psychology Review · doi:10.1016/j.cpr.2013.06.001 · Cited by 648 · see citing works
Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan
Franke, B., Michelini, G., Asherson, P., Banaschewski, T., Bilbow, A., Buitelaar, J. K., Cormand, B., Faraone, S. V., Ginsberg, Y., Haavik, J., et al. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.08.001 · Cited by 643 · see citing works
Frontal-subcortical circuitry and behavior
Bonelli, R. M., & Cummings, J. L. (2007) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2007.9.2/rbonelli · Cited by 613 · see citing works
Reichenberg, A., & Harvey, P. D. (2007) · Psychological Bulletin · doi:10.1037/0033-2909.133.5.833 · Cited by 536 · see citing works
The genetics of attention deficit/hyperactivity disorder in adults, a review
on behalf of the International Multicentre persistent ADHD CollaboraTion (IMpACT), Franke, B., Faraone, S. V., Asherson, P., Buitelaar, J., Bau, C. H. D., Ramos-Quiroga, J. A., Mick, E., Grevet, E. H., Johansson, S., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.138 · Cited by 432 · see citing works
A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD)
Luo, Y., Weibman, D., Halperin, J. M., & Li, X. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00042 · Cited by 394 · see citing works
“…(Tannock et al., 1995; Barkley, 1997; Sonuga-Barke, 2003; Martinussen et al., 2005; Martinussen and Tannock, 2006; Rogers et al., 2011; Mawjee et al., 2017; Simone et al., 2018); (2) cognitive-energetic model (CEM; Sergeant, 2000); and (3) neurodevelopmental model (Halperin and Schulz, 2006).”
BackgroundInfluentialSelf-citationToplak, M. E., Bucciarelli, S. M., Jain, U., & Tannock, R. (2008) · Child Neuropsychology · doi:10.1080/09297040802070929 · Cited by 401 · see citing works
Posner, M. I. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1417.011 · Cited by 345 · see citing works
Sonuga‐Barke, E. J. S., & Halperin, J. M. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2009.02195.x · Cited by 320 · see citing works
Self-citationBeauchaine, T. P., & McNulty, T. (2013) · Development and Psychopathology · doi:10.1017/s0954579413000746 · Cited by 310 · see citing works
Shaw, P., Malek, M., Watson, B., Greenstein, D., de Rossi, P., & Sharp, W. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.04.007 · Cited by 303 · see citing works
“It has been argued that structural and functional normalization of the cortex is the mechanism underpinning symptomatic remission in ADHD (22, 53).”
BackgroundMcLaughlin, K. A., Sheridan, M. A., Winter, W., Fox, N. A., Zeanah, C. H., & Nelson, C. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.08.016 · Cited by 288 · see citing works
“Abnormalities in frontostriatal function are central to theoretical conceptualizations of cognitive deficits in ADHD, including working memory and response selection and inhibition (9,72,73).”
BackgroundSacco, R., Camilleri, N., Eberhardt, J., Umla‐Runge, K., & Newbury‐Birch, D. (2022) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-022-02131-2 · Cited by 302 · see citing works
“This trend may be explained by agerelated development in the prefrontal cortex [75].”
Beauchaine, T. P., Klein, D. N., Crowell, S. E., Derbidge, C. M., & Gatzke‐Kopp, L. M. (2009) · Development and Psychopathology · doi:10.1017/s0954579409000418 · Cited by 263 · see citing works
“We do not consider frontal dysfunction as an early predisposing vulnerability because these brain regions mature very late in adolescence, and are therefore less likely to underlie the early expression of impulsivity (Halperin & Schulz, 2006).”
BackgroundSwanson, J., Baler, R. D., & Volkow, N. D. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.160 · Cited by 252 · see citing works
“The developmental courses of behavioral manifestations of the disorder (symptoms) and neuropsychological performance (executive function deficits) have been evaluated in prospective studies of children with ADHD followed into adulthood, and some suggested attenuation in executive functioning deficits among patients wi…”
BackgroundHalperin, J. M., Trampush, J. W., Miller, C. J., Marks, D. J., & Newcorn, J. H. (2008) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2008.01926.x · Cited by 252 · see citing works
Self-citationBasal Ganglia Volume and Shape in Children With Attention Deficit Hyperactivity Disorder
Qiu, A., Crocetti, D., Adler, M. C., Mahone, E. M., DENCKLA, M. B., Miller, M. I., & Mostofsky, S. H. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08030426 · Cited by 250 · see citing works
“Anomalous basal ganglia structure and function may thereby contribute to difficulty with response control that is characteristic of ADHD (3, 4).”
Durston, S., van Belle, J., & de Zeeuw, P. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.07.037 · Cited by 248 · see citing works
Halperin, J. M., & Healey, D. M. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.07.006 · Cited by 237 · see citing works
Self-citationTrait Impulsivity and the Externalizing Spectrum
Beauchaine, T. P., Zisner, A. R., & Sauder, C. L. (2017) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-021815-093253 · Cited by 230 · see citing works
Skirrow, C., McLoughlin, G., Kuntsi, J., & Asherson, P. (2009) · Expert Review of Neurotherapeutics · doi:10.1586/ern.09.2 · Cited by 217 · see citing works
Ten good reasons to consider biological processes in prevention and intervention research
Beauchaine, T. P., Neuhaus, E., Brenner, S. L., & Gatzke-Kopp, L. (2008) · Development and Psychopathology · doi:10.1017/s0954579408000369 · Cited by 215 · see citing works
“The mesolimbic DA system, which develops very early in life, is modulated in adolescence and adulthood by the mesocortical DA system (see Halperin & Schulz, 2006; Spear, 2007), a frontal neural network that exhibits experience-dependent development into young adulthood (see above).”
BackgroundBrain adaptation and alternative developmental trajectories
Johnson, M. H., Jones, E. J. H., & Gliga, T. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000073 · Cited by 213 · see citing works
“In addition to Johnson (2012), other authors have previously proposed a role for the PFC in compensating for the core deficits in other brain systems that may underlie ADHD (Fassbender & Schweitzer, 2006; Halperin & Schulz, 2006).”
Greven, C. U., Bralten, J., Mennes, M., O’Dwyer, L., van Hulzen, K. J. E., Rommelse, N., Schweren, L. J. S., Hoekstra, P. J., Hartman, C. A., Heslenfeld, D., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.3162 · Cited by 198 · see citing works
Proal, E. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.117 · Cited by 207 · see citing works
“This supports the suggestion that symptom amelioration and diagnostic remission may result in part from compensatory maturation of frontal-thalamiccerebellar circuits.(102,104)”
BackgroundAnnual Research Review: Optimal outcomes of child and adolescent mental illness
Costello, E. J., & Maughan, B. (2014) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12371 · Cited by 204 · see citing works
“Findings on the role of executive functions (Halperin & Schulz, 2006) are less consistent, but a number of studies have noted that higher IQ is associated with more positive treatment response and later outcomes.”
BackgroundYang, Y., Shields, G. S., Zhang, Y., Wu, H., Chen, H., & Romer, A. L. (2022) · Clinical Psychology Review · doi:10.1016/j.cpr.2022.102194 · Cited by 201 · see citing works
Executive function and developmental disorders: the flip side of the coin
Johnson, M. H. (2012) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2012.07.001 · Cited by 190 · see citing works
Johnson, K. A., Robertson, I. H., Barry, E., Mulligan, A., Dáibhis, A., Daly, M., Watchorn, A., Gill, M., & Bellgrove, M. A. (2008) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2008.01936.x · Cited by 192 · see citing works
Developmental Twin Study of Attention Problems: High Heritabilities Throughout Development
Chang, Z., Lichtenstein, P., Asherson, P. J., & Larsson, H. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.287 · Cited by 194 · see citing works
Does Childhood Executive Function Predict Adolescent Functional Outcomes in Girls with ADHD?
Miller, M. R., & Hinshaw, S. P. (2009) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-009-9369-2 · Cited by 189 · see citing works
“Others have posited that ADHD results from noncortical dysfunction but that prefrontally-mediated mechanisms account for symptom reduction and potential improvements in EF throughout development (Halperin and Schulz 2006).”
BackgroundCastellanos, F. X., & Aoki, Y. Y. (2016) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2016.03.004 · Cited by 185 · see citing works
Molina, B. S. G., & Pelham, W. E. (2014) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032813-153722 · Cited by 186 · see citing works
“For example, the development of “top down” neural systems with age has been hypothesized to account for the post-childhood reduction of ADHD symptoms that occurs for some (Halperin and Schulz 2006) and, if Annu Rev Clin Psychol.”
BackgroundAbnormal cerebral cortex structure in children with ADHD
Wolosin, S. M., Richardson, M. E., Hennessey, J. G., DENCKLA, M. B., & Mostofsky, S. H. (2007) · Human Brain Mapping · doi:10.1002/hbm.20496 · Cited by 177 · see citing works
“Several investigators have posited that observed deficits in executive control in ADHD point to dysfunction within frontal-subcortical circuits [Denckla and Reiss, 1997; Halperin and Schulz, 2006; Heilman, 1991].”
BackgroundDevelopment of ADHD: Etiology, Heterogeneity, and Early Life Course
Nigg, J. T., Sibley, M. H., Thapar, A., & Karalunas, S. L. (2020) · Annual Review of Developmental Psychology · doi:10.1146/annurev-devpsych-060320-093413 · Cited by 184 · see citing works
“…life (e.g., emotional reactivity, or disrupted reward-motivational responding), which sufficiently strong and timely consolidation of top down control (and the corresponding neural maturation), for some individuals, enables stable adjustment during and after adolescence (Halperin & Schulz, 2006).”
BackgroundResultAlmeida, L. G., Ricardo-Garcell, J., Prado, H., Barajas, L., Fernández-Bouzas, A., Ávila, D., & Martínez, R. B. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.04.026 · Cited by 165 · see citing works
Kuntsi, J., Wood, A. C., Johnson, K. A., Andreou, P., Arias-Vasquez, A., Buitelaar, J. K., Rommelse, N. N. J., Sergeant, J. A., Sonuga-Barke, E. J., Uebel, H., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.139 · Cited by 162 · see citing works
European Journal of Psychotraumatology
Olff, M., & Bindslev, A. (2011) · European Journal of Psychotraumatology · doi:10.3402/ejpt.v2i0.15546 · Cited by 156 · see citing works
Hoza, B., Smith, A. L., Shoulberg, E. K., Linnea, K. S., Dorsch, T. E., Blazo, J., Alerding, C. M., & McCabe, G. P. (2014) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-014-9929-y · Cited by 157 · see citing works
Friedman, L. A., & Rapoport, J. L. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.11.007 · Cited by 154 · see citing works
Imaging the ADHD brain: disorder-specificity, medication effects and clinical translation
Rubia, K., Alegria, A., & Brinson, H. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2014.907526 · Cited by 146 · see citing works
“The findings are also in line with theories of prominently subcortical deficits in pediatric ADHD, which may lead to consequential frontal abnormalities later on in adult ADHD [90].”
ResultPosner, M. I. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2011.12.040 · Cited by 151 · see citing works
“There is evidence that ADHD may involve a deficit in alerting either alone (Halperin and Schulz, 2006) or in conjunction with an executive deficit (Johnson et al.”
Sarver, D. E., Rapport, M. D., Kofler, M. J., Raiker, J. S., & Friedman, L. M. (2015) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-015-0011-1 · Cited by 149 · see citing works
“…the more recent subcortical deficit model describes hyperactivity as a manifestation of early occurring and static subcortical impairment rather than an outcome or correlate of underdeveloped executive functions such as inhibition or working memory (Halperin and Schulz 2006; Halperin et al. 2008).”
BackgroundPreventive Interventions for ADHD: A Neurodevelopmental Perspective
Halperin, J. M., Bedard, A., & Curchack, J. T. (2012) · Neurotherapeutics · doi:10.1007/s13311-012-0123-z · Cited by 151 · see citing works
Self-citationCognitive and neurophysiological markers of ADHD persistence and remission
Cheung, C. H. M., Rijsdijk, F., McLoughlin, G., Brandeis, D., Banaschewski, T., Asherson, P., & Kuntsi, J. (2016) · British Journal of Psychiatry · doi:10.1192/bjp.bp.114.145185 · Cited by 146 · see citing works
“…a distinction between potential top-down cognitive control and bottom-up arousal regulation was also made in a previous developmental ADHD model, 36,37 the pattern 552 observed in our data is not consistent with the model’s predictions of how the impairments map onto persistence and remittance.”
Cortical activity patterns in ADHD during arousal, activation and sustained attention
Loo, S. K., Hale, T. S., Macion, J., Hanada, G., McGough, J. J., McCracken, J. T., & Smalley, S. L. (2009) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2009.04.013 · Cited by 146 · see citing works
Intraindividual Variability in ADHD and Its Implications for Research of Causal Links
Kuntsi, J., & Klein, C. (2011) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2011_145 · Cited by 138 · see citing works
“Recent models, such as the Developmental and Arousal-Attention models, which incorporate RT variability together with a second proposed underlying process, offer one solution to the conundrum of the “bigger picture”: how to incorporate the findings on RT variability with the findings on other cognitive impairments in…”
BackgroundResultInfluentialNeurobiology of Attention Deficit Hyperactivity Disorder
Kieling, C., Kieling, R. R., Tannock, R., & Castellanos, F. X. (2008) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2007.11.012 · Cited by 138 · see citing works
Coghill, D., Hayward, D. A., Rhodes, S., Grimmer, C., & Matthews, K. (2013) · Psychological Medicine · doi:10.1017/s0033291713001761 · Cited by 137 · see citing works
“Based on the developmental theories of Halperin & Schulz (2006) described above, we further hypothesized that, for the ADHD group, symptom reduction would be associated with improved performance on tasks with high but not low executive function demands.”
BackgroundMethodResultInfluentialSelf-regulation: Brain, cognition, and development.
Berger, A. (2011) · American Psychological Association eBooks · doi:10.1037/12327-000 · Cited by 142 · see citing works
Brain alterations in adult ADHD: Effects of gender, treatment and comorbid depression
Onnink, A. M. H., Zwiers, M. P., Hoogman, M., Mostert, J. C., Kan, C. C., Buitelaar, J., & Franke, B. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.11.011 · Cited by 131 · see citing works
“This finding is in line with the hypothesis of Halperin and Schulz (2006) that subcortical dysfunction that manifests early in life, remains static throughout the lifetime, and is not associated with the remission of symptomatology.”
ResultDoes neurocognitive functioning predict future or persistence of ADHD? A systematic review
van Lieshout, M., Luman, M., Buitelaar, J., Rommelse, N. N. J., & Oosterlaan, J. (2013) · Clinical Psychology Review · doi:10.1016/j.cpr.2013.02.003 · Cited by 133 · see citing works
“…a non-cortical (for example basal ganglia, cerebellum: not involving neocortical areas) neural dysfunction that is present early in life, remains relatively stable throughout the lifetime, and is not associated with remission of symptoms that often occurs in adolescence (Halperin & Schulz, 2006).”
BackgroundMethodResultInfluentialSleep disturbances in adolescents with ADHD: A systematic review and framework for future research
Lunsford-Avery, J. R., Krystal, A. D., & Kollins, S. H. (2016) · Clinical Psychology Review · doi:10.1016/j.cpr.2016.10.004 · Cited by 131 · see citing works
“Finally, disparate developmental trajectories of ADHD may begin to diverge during adolescence (Halperin & Schulz, 2006), suggesting that deviations in biological processes occurring during this period may contribute to variable prognosis and clinical outcomes within the ADHD population.”
BackgroundBeauchaine, T. P., Neuhaus, E., Zalewski, M., Crowell, S. E., & Potapova, N. V. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000459 · Cited by 129 · see citing works
“As outlined below, such modulation may be vulnerable to allostatic effects given experience-dependent development of both midbrain and cortical DA systems (see Arnsten, 2009; Halperin & Schulz, 2006; Spear, 2007; Sullivan & Brake, 2003).”
BackgroundRisky behavior in gambling tasks in individuals with ADHD–a systematic literature review
Groen, Y., Gaastra, G. F., Lewis-Evans, B., & Tucha, O. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074909 · Cited by 127 · see citing works
“The prefrontal recovery hypothesis [73] postulates that the reduction of ADHD symptoms during adolescence is related to the degree in which prefrontal cognitive control functions (‘cold’ decisionmaking) compensate for primary and persistent subcortical deficits (‘hot’ decision-making).”
BackgroundSiddique, S., Banerjee, M., Ray, M. R., & Lahiri, T. (2010) · European Journal of Pediatrics · doi:10.1007/s00431-010-1379-0 · Cited by 127 · see citing works
“It has been hypothesized that ADHD is due to noncortical dysfunction that manifests early in ontogeny [ 14 ], but the precise etiology of ADHD is currently unknown.”
BackgroundShaw, P., De Rossi, P., Watson, B., Wharton, A., Greenstein, D., Raznahan, A., Sharp, W., Lerch, J. P., & Chakravarty, M. M. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.05.003 · Cited by 126 · see citing works
Assessment of Attention in Preschoolers
Mahone, E. M., & Schneider, H. E. (2012) · Neuropsychology Review · doi:10.1007/s11065-012-9217-y · Cited by 128 · see citing works
“The trajectory of functional development, however, is nonlinear, and progresses in a region-specific manner that coincides with maturation of different brain systems (Halperin and Schulz 2006).”
BackgroundBerger, I., Slobodin, O., & Cassuto, H. (2016) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acw101 · Cited by 122 · see citing works
“The first is a subcortical dysfunction that persists across development and the second is a frontal dysfunction that improves with time (Halperin & Schulz, 2006).”
Hartman, C. A., Geurts, H. M., Franke, B., Buitelaar, J. K., & Rommelse, N. N. J. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.003 · Cited by 111 · see citing works
Rommelse, N. N. J., Altink, M. E., Oosterlaan, J., Beem, L., Buschgens, C. J. M., Buitelaar, J. K., & Sergeant, J. A. (2007) · Behavior Genetics · doi:10.1007/s10519-007-9186-8 · Cited by 110 · see citing works
“…by the cerebellum, basal ganglia and their reciprocal connections with the cerebral cortex (Handy et al. 2003; Harrington et al. 1998; Ivry 1996; Nenadic et al. 2003), subcortical regions in addition to cortical regions might be important in the etiology of ADHD (Halperin and Schulz 2006).”
BackgroundKaralunas, S. L., Gustafsson, H. C., Dieckmann, N. F., Tipsord, J., Mitchell, S. H., & Nigg, J. T. (2017) · Journal of Abnormal Psychology · doi:10.1037/abn0000292 · Cited by 104 · see citing works
“…functioning) during middle childhood and adolescence contributes to ADHD symptom improvements observed during this same time period for some children (Doehnert, Brandeis, Imhof, Drechsler, & Steinhausen, 2010; El-Sayed, Larsson, Persson, Santosh, & Rydelius, 2003; Halperin & Schulz, 2006).”
Karalunas, S. L., Huang-Pollock, C. L., & Nigg, J. T. (2012) · Neuropsychology · doi:10.1037/a0029936 · Cited by 104 · see citing works
“Indeed, each of these component processes have been variously hypothesized to be involved in ADHD (Banaschewski et al., 2008; Halperin & Schulz, 2006; Hurks et al., 2005; Klimkeit, Mattingley, Sheppard, Lee, & Bradshaw, 2005; Lajoie et al., 2005; Sergeant, 2000; Sergeant & Scholten, 1985; Steger et…”
Kuntsi, J., Pinto, R., Price, T. S., van der Meere, J. J., Frazier-Wood, A. C., & Asherson, P. (2014) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-013-9771-7 · Cited by 106 · see citing works
“The two cognitive impairments in ADHD may also interplay throughout development, leading to different outcomes for ADHD as individuals pass from childhood into adulthood (Halperin and Schulz 2006; Halperin et al. 2008).”
BackgroundMethodFrancx, W., Oldehinkel, M., Oosterlaan, J., Heslenfeld, D., Hartman, C. A., Hoekstra, P. J., Franke, B., Beckmann, C. F., Buitelaar, J. K., & Mennes, M. (2015) · Cortex · doi:10.1016/j.cortex.2015.08.012 · Cited by 102 · see citing works
“…c t Background: One neurodevelopmental theory hypothesizes remission of attention-deficit/ hyperactivity disorder (ADHD) to result from improved prefrontal top-down control, while ADHD, independent of the current diagnosis, is characterized by stable non-cortical deficits (Halperin & Schulz, 2006).”
BackgroundHow Do Trait Dimensions Map onto ADHD Symptom Domains?
Martel, M. M., Nigg, J. T., & von Eye, A. (2009) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-008-9255-3 · Cited by 105 · see citing works
“As a result, top-down circuitry might have an increasingly important influence on descending neural circuitry during late adolescence (Halperin and Schultz 2006), allowing individuals to more efficiently control affect and affectively-driven behavior such as hyperactivity (Sowell et al.”
InfluentialHalperin, J. M., Marks, D. J., Bedard, A.-C. V., Chacko, A., Curchack, J. T., Yoon, C. A., & Healey, D. M. (2013) · Journal of Attention Disorders · doi:10.1177/1087054711435681 · Cited by 106 · see citing works
“As such, it has been hypothesized that enhancement of experience-dependent neurodevelopment can be used to facilitate recovery or a diminution of symptoms over the life span (Halperin & Healey, 2011; Halperin & Schulz, 2006).”
BackgroundSelf-citationAre Motor Inhibition and Cognitive Flexibility Dead Ends in ADHD?
Rommelse, N. N. J., Altink, M. E., de Sonneville, L. M. J., Buschgens, C. J. M., Buitelaar, J., Oosterlaan, J., & Sergeant, J. A. (2007) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-007-9146-z · Cited by 103 · see citing works
“It might be that the (pre)frontal lobes are not causally involved in the disorder, but contribute to the age related recovery of symptoms frequently observed in ADHD patients (Halperin and Schulz 2006).”
BackgroundMetin, B., Roeyers, H., Wiersema, J. R., van der Meere, J. J., Thompson, M. J. J., & Sonuga-Barke, E. J. S. (2013) · Neuropsychology · doi:10.1037/a0031533 · Cited by 103 · see citing works
Time Reproduction in Children With ADHD and Their Nonaffected Siblings
Rommelse, N. N. J., Oosterlaan, J., Buitelaar, J. K., Faraone, S. V., & Sergeant, J. A. (2007) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e3180335af7 · Cited by 103 · see citing works
“(Biederman et al., 2000; Faraone et al., 2006; Halperin and Schulz, 2006).”
BackgroundResultInfluentialImplementation Intentions Facilitate Response Inhibition in Children with ADHD
Gawrilow, C., & Gollwitzer, P. M. (2008) · Cognitive Therapy and Research · doi:10.1007/s10608-007-9150-1 · Cited by 103 · see citing works
“…a somewhat incoherent picture, with some studies failing to find differences on several measures of executive functioning and other studies only allowing vague inferences regarding the exact nature of the executive dysfunction observed (Halperin & Schulz, 2006; Wu, Anderson, & Castiello, 2006).”
Cognitive enhancers for the treatment of ADHD
Bidwell, L. C., McClernon, F. J., & Kollins, S. H. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.05.002 · Cited by 101 · see citing works
“Weaknesses in these prefrontal regions are thought to interact with dysfunction in subcortical regions, including striatal regions and the cerebellum, in order produce requisite EF deficits in ADHD patients (Halperin and Schulz, 2006).”
BackgroundAn Open Trial of a Metacognitive Executive Function Training for Young Children With ADHD
Tamm, L., Nakonezny, P. A., & Hughes, C. W. (2014) · Journal of Attention Disorders · doi:10.1177/1087054712445782 · Cited by 98 · see citing works
Berwid, O. G., & Halperin, J. M. (2012) · Current Psychiatry Reports · doi:10.1007/s11920-012-0297-4 · Cited by 99 · see citing works
“deficits through ‘top down’ regulatory control [14].”
Self-citationKing, J. A., Colla, M., Braß, M., Heuser, I., & von Cramon, D. (2007) · Behavioral and Brain Functions · doi:10.1186/1744-9081-3-42 · Cited by 102 · see citing works
Integrating Impairments in Reaction Time and Executive Function Using a Diffusion Model Framework
Karalunas, S. L., & Huang‐Pollock, C. L. (2013) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-013-9715-2 · Cited by 98 · see citing works
“All have been hypothesized to be involved in ADHD (Banaschewski et al. 2008; Halperin and Schulz 2006; Hurks et al. 2005; Klimkeit et al. 2005; Lajoie et al. 2005; Sergeant 2000; Sergeant and Scholten 1985; Steger et al. 2001).”
Shephard, E., Zuccolo, P. F., Idrees, I., Godoy, P. B. G., Salomone, E., Ferrante, C., Sorgato, P., Catão, L. F. C. C., Goodwin, A., Bolton, P., et al. (2021) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2021.03.016 · Cited by 96 · see citing works
Geissler, J. M., Romanos, M., Hegerl, U., & Hensch, T. (2014) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-014-0144-z · Cited by 96 · see citing works
“Other authors suspected structural alterations in regions involved in modulating arousal (e.g. formatio reticularis; Halperin and Schulz 2006) to be disruptive to vigilance regulation in ADHD.”
BackgroundExecutive function predicts school readiness in autistic and typical preschool children
Pellicano, E., Kenny, L., Brede, J., Klaric, E., Lichwa, H., & McMillin, R. (2017) · Cognitive Development · doi:10.1016/j.cogdev.2017.02.003 · Cited by 97 · see citing works
Cerebellar involvement in autism and ADHD
Bruchhage, M. M. K., Bucci, M. P., & Becker, E. B. E. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64189-2.00004-4 · Cited by 94 · see citing works
An Evolutionary Perspective on Learning Disability in Mathematics
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“There is considerable heterogeneity within these diagnostic categories which may, in part, be due to variation in the underlying brain systems that contribute to the behavioral and cognitive features of these disorders (e.g., Halperin & Schulz, 2006).”
BackgroundChacko, A., Kofler, M., & Jarrett, M. (2014) · Clinical Child and Family Psychology Review · doi:10.1007/s10567-014-0171-5 · Cited by 93 · see citing works
“Finally, some models hypothesize that executive functioning impairments are unrelated to core ADHD behavioral symptoms (Halperin and Schulz 2006), but rather serve ontogenetic compensatory mechanisms (Rajendran et al. 2013).”
Kofler, M. J., Raiker, J. S., Sarver, D. E., Wells, E. L., & Soto, E. F. (2016) · Clinical Psychology Review · doi:10.1016/j.cpr.2016.04.004 · Cited by 88 · see citing works
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“It has been hypothesized that such an autonomic imbalance -low parasympathetic activity and a relative sympathetic dominance- reflects low heart rate variability, a marker for prefrontal hypoactivity (Thayer and Sternberg, 2006) as seen in ADHD (Arnsten, 1998; Halperin and Schulz, 2006; Himelstein et al., 2000; Valera…”
BackgroundThe hierarchical factor model of ADHD: invariant across age and national groupings?
Toplak, M. E., Sorge, G. B., Flora, D. B., Chen, W., Banaschewski, T., Buitelaar, J. K., Ebstein, R. P., Eisenberg, J., Franke, B., Gill, M., et al. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2011.02500.x · Cited by 83 · see citing works
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Parameterization-Invariant Shape Comparisons of Anatomical Surfaces
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“…bases upon deficient prefrontal control of striatal, cerebellar and limbic neural activation patterns as well as dysfunctional interconnections, which together affect cognitive control, motivation, attention, and affect regulation (Halperin and Schulz 2006; Nigg and Casey 2005; Sonuga-Barke 2002).”
BackgroundInfluentialMaturational delay in ADHD: evidence from CPT
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Adolescent Attention-Deficit/Hyperactivity Disorder: Understanding Teenage Symptom Trajectories
Shaw, P., & Sudre, G. P. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.06.004 · Cited by 85 · see citing works
“For example, it has been argued that while ADHD is caused by subcortical anomalies which persist throughout the lifespan, its variable clinical course is determined by plasticity of the cerebral cortex (46).”
BackgroundToward a revised nosology for attention-deficit/hyperactivity disorder heterogeneity
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Utility of capromab pendetide (ProstaScint) imaging in the management of prostate cancer.
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- Authors
- Halperin, J. M., & Schulz, K. P.
- Affiliations
- Queens College, CUNY (US)
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Psychological Bulletin
- Published
- 2006
- Volume
- 132
- Issue
- 4
- Pages
- 560-581
- ISSN
- 0033-2909 (ISSN-L)
- 1939-1455
- OpenAlex
- W2139377807
- Semantic Scholar
- 9b63dbee33341e428d6c3a9a7c386b7dd42c7191
- Cited by
- 446
- References
- 298
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 21 · 2023: 14 · 2022: 22 · 2021: 21 · 2020: 34 · 2019: 14 · 2018: 18 · 2017: 26 · 2016: 30 · 2015: 25 · 2014: 30 · 2013: 35 · 2012: 25
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- William T. Grant Foundation (97183497)
- National Institute of Mental Health (RO1 MH60698; RO1 MH068206; R21 MH066360)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, prefrontal cortex, neurodevelopmental model, striatum, symptom remission, ADHD pathophysiology
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Humans, Prefrontal Cortex
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