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Brain regions affected by ADHD

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Brain regions affected by ADHD

1. Brain regions affected by ADHD

ADHD is associated with changes in various regions of the brain:

  • PFC
    • DlPFC
    • MPFC
    • OlPFC
  • Basal ganglia1
    • Striatum
      • Nucleus caudates
      • Thalamus
  • Cerebellum1
  • Corpus callosum1
  • Largest reductions in gray matter in:2
    • Frontal-parietal brain regions
    • Corpus callosum
    • Limbic system
      This includes:3
      • Corpus mamillare
        • Memory formation, in the context of the Papez neuron circle
        • Sexual functions
      • Cingulate gyrus
        • Vegetative functions
        • Psychomotor and locomotor drive
      • Parahippocampal gyrus
        • Primarily transmits information from the limbic system to the hippocampus
        • Memory formation
      • Hippocampus
        • Memory formation
        • Vegetative and emotional functions
      • Amygdala
        • Storage of emotionally moving memory content
        • Vegetative and sexual functions
  • Significant hypoactivation in2
    • Several frontal-temporal brain regions
    • Right postcentral gyrus
    • Left insula
    • Corpus callosum

An analysis of car accidents in unaffected people found a correlation between percuneus volume and car accidents that is consistent with changes in ADHD.4

2. Volume changes in brain regions with ADHD

In ADHD, the volume of various brain regions is altered.

In children with ADHD, MRI studies found that compared to those not affected

  • Total brain volume reduced
    • (by 4 %)5
  • Caudates downsized56
  • PFC7
    • Anterior PFC reduced5
    • Orbital PFC reduced, predominantly on the right8
  • Inferior dorsolateral frontal region8
  • Basal ganglia
    • Right7
    • Striatum reduced in size8
    • Striatum enlarged9
    • Globus pallidus reduced in size5 8
  • Cerebellum
    • Reduced 67
    • Enlarged9
  • Central vermis area, predominantly reduced on the right58
  • ACC
    • Reduced, mostly underactivated8
  • Corpus callosum7
    • Splenium (beam bulge) reduced8
  • Putamen changed6
  • Thalamus changes6 or hypoactive10

The effects are stronger in boys than in girls, which correlates with the Polygenic Risk Score.6

One study investigated structural and functional changes in the glymphatic system in treatment-free children with ADHD. The cerebral volume of the Virchow-Robin spaces was increased by 32 % (15.514 mL vs. 11.702 mL).11

Interestingly, the reduction in the size of certain brain regions that is usually observed from the age of 60 appears to be less pronounced in ADHD. This is discussed as a neuroprotective factor of ADHD. It remains to be seen whether this is a consequence of ADHD itself or of stimulant treatment.
This is particularly significant in brain regions in which a strong loss of volume correlates with cognitive impairment and Alzheimer’s, such as the hippocampus and amygdala.12

3. White substance

The white matter consists mainly of neurons and their extensions (axons). Myelinated axons look white.

A meta-analysis of 129 studies with n = 6739 ADHD sufferers and n = 6476 controls found conspicuous changes in the posterior interhemispheric connections responsible for the cognitive and motor functions affected by ADHD:13

  • reduced fractional anisotropy (FA) in the projection, commissural and association pathways, which correlated with symptom severity and cognitive deficits
  • consistently reduced FA in the splenium and corpus callosum, extending to the cingulum
  • lower FA was only found in old age, not in children
    • possibly due to the late development of the callosal fibers

In ADHD, a significantly increased axial diffusivity was found in the right cingulum bundle.14

Children with ADHD showed microstructural changes and alterations in long-range white matter connections. Learning problems and hyperactivity/impulsivity correlated negatively with the mean FA value in the right forceps major (the occipital part of the fibers of the corpus callosum), the left IFOF and the left genu capsulae internae.15

4. Myelination

One study found no differences in ADHD with regard to myelin content in the entire brain.16
ADHD correlated with

  • a higher mean myelin volume fraction in
    • bilateral inner capsule
    • outer capsule
    • Corona radiata
    • Corpus callosum
    • left tapetum
    • left superior fronto-occipital fascia
    • right cingulum

  1. Biederman, Faraone (2005): Attention-deficit hyperactivity disorder. Lancet. 2005 Jul 16-22;366(9481):237-48. doi: 10.1016/S0140-6736(05)66915-2. Erratum in: Lancet. 2006 Jan 21;367(9506):210. PMID: 16023516. REVIEW

  2. Yu M, Gao X, Niu X, Zhang M, Yang Z, Han S, Cheng J, Zhang Y (2023): Meta-analysis of structural and functional alterations of brain in patients with attention-deficit/hyperactivity disorder. Front Psychiatry. 2023 Jan 6;13:1070142. doi: 10.3389/fpsyt.2022.1070142. PMID: 36683981; PMCID: PMC9853532. METASTUDIE

  3. DocCheck Flexikon: Limbisches System

  4. Putra HA, Park K, Oba H, Yamashita F (2023): Adult attention-deficit/hyperactivity disorder traits in healthy adults associated with brain volumetric data identify precuneus involvement in traffic crashes. Sci Rep. 2023 Dec 18;13(1):22466. doi: 10.1038/s41598-023-49907-3. PMID: 38105321; PMCID: PMC10725881.

  5. Castellanos (2001): Neuroimaging studies of ADHD. In Solanto, Arnsten, Castellanos (Herausgeber): Stimulant drugs and ADHD: Basic and clinical neuroscience (p. 243–258). zitiert nach Solanto (2002): Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research. Behav Brain Res. 2002 Mar 10;130(1-2):65-71.

  6. Mooney, Bhatt, Hermosillo, Ryabinin, Nikolas, Faraone, Fair, Wilmot, Nigg (2020): Smaller total brain volume but not subcortical structure volume related to common genetic risk for ADHD. Psychol Med. 2020 Jan 24;1-10. doi: 10.1017/S0033291719004148. PMID: 31973781.

  7. Regan SL, Williams MT, Vorhees CV (2022): Review of rodent models of attention deficit hyperactivity disorder. Neurosci Biobehav Rev. 2022 Jan;132:621-637. doi: 10.1016/j.neubiorev.2021.11.041. PMID: 34848247; PMCID: PMC8816876.)

  8. Barkley (2014): The Importance of Emotion in ADHD; https://drive.google.com/file/d/0B885LHMHOu5BWmR1YlNoOElCLTg/view?resourcekey=0-lBjUELS_pba99fW5nP5vng unter Verweis auf Cortese, Kelly, Chabernaud, Proal, Di Martino, Milham, Castellanos (2012): Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. Am J Psychiatry. 2012 Oct;169(10):1038-55. doi: 10.1176/appi.ajp.2012.11101521. PMID: 22983386; PMCID: PMC3879048.

  9. Chang JC, Lin HY, Gau SS (2023): Distinct developmental changes in regional gray matter volume and covariance in individuals with attention-deficit hyperactivity disorder: A longitudinal voxel-based morphometry study. Asian J Psychiatr. 2023 Dec 12;91:103860. doi: 10.1016/j.ajp.2023.103860. PMID: 38103476.

  10. Källstrand J, Niklasson K, Lindvall M, Claesdotter-Knutsson E (2022): Reduced thalamic activity in ADHD under ABR forward masking conditions. Appl Neuropsychol Child. 2022 Dec 16:1-7. doi: 10.1080/21622965.2022.2155520. PMID: 36524942.

  11. Chen Y, Wang M, Su S, Dai Y, Zou M, Lin L, Qian L, Li X, Zhang H, Liu M, Chu J, Yang J, Yang Z (2023): Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder. Eur Radiol. 2023 Sep 6. doi: 10.1007/s00330-023-10220-2. PMID: 37673963.

  12. Dutta CN, Christov-Moore L, Ombao H, Douglas PK (2022): Neuroprotection in late life attention-deficit/hyperactivity disorder: A review of pharmacotherapy and phenotype across the lifespan. Front Hum Neurosci. 2022 Sep 26;16:938501. doi: 10.3389/fnhum.2022.938501. PMID: 36226261; PMCID: PMC9548548.

  13. Parlatini V, Itahashi T, Lee Y, Liu S, Nguyen TT, Aoki YY, Forkel SJ, Catani M, Rubia K, Zhou JH, Murphy DG, Cortese S (2023): White matter alterations in Attention-Deficit/Hyperactivity Disorder (ADHD): a systematic review of 129 diffusion imaging studies with meta-analysis. Mol Psychiatry. 2023 Jul 21. doi: 10.1038/s41380-023-02173-1. PMID: 37479785.

  14. Hu R, Tan F, Chen W, Wu Y, Jiang Y, Du W, Zuo Y, Gao B, Song Q, Miao Y (2023): Microstructure abnormalities of the diffusion quantities in children with attention-deficit/hyperactivity disorder: an AFQ and TBSS study. Front Psychiatry. 2023 Aug 22;14:1237113. doi: 10.3389/fpsyt.2023.1237113. PMID: 37674550; PMCID: PMC10477457.

  15. Zhou R, Dong P, Chen S, Qian A, Tao J, Zheng X, Cheng J, Yang C, Huang X, Wang M (2022): The long-range white matter microstructural alterations in drug-naive children with ADHD: A tract-based spatial statistics study. Psychiatry Res Neuroimaging. 2022 Oct 7;327:111548. doi: 10.1016/j.pscychresns.2022.111548. PMID: 36279811. n = 98

  16. Lin L, Chen Y, Dai Y, Yan Z, Zou M, Zhou Q, Qian L, Cui W, Liu M, Zhang H, Yang Z, Su S (2023): Quantification of myelination in children with attention-deficit/hyperactivity disorder: a comparative assessment with synthetic MRI and DTI. Eur Child Adolesc Psychiatry. 2023 Sep 15. doi: 10.1007/s00787-023-02297-3. PMID: 37712949.

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