Minimal Brain Damage
Contents
1 How minimal?
Historically, when the term Minimal Brain Damage was in use, it meant brain damage that could not at that time be detected on current scanning technology, nor even in post-mortem gross anatomy examination. Modern brain imaging studies now detect the presence of abnormalities in structure (smaller size) and function (hypoactivation) of critical brain regions related to dopamine (DA) in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) [13].
2 Specific Deficits
Lou [8] and Volpe [14] suggest an excitotoxicity hypothesis to explain how ‘minimal brain damage’ may not be detected by earlier brain imaging techniques: the damage might preferentially affect late-developing granular cells and other interneurons and pathologically reduce the population of neurons that will later differentiate into specific brain structures. Thus, the morphology of the structure and overall brain will be normal, but smaller. The striatum was specifically highlighted because it is rich in dopaminergic synapses, is vulnerable to perinatal hypoxic complications, and if damaged, produces hyperactivity and poor inhibitory control [8].
This hypothesis has gained further support with modern structural and functional neuroimaging studies showing ADHD subjects to have small volume reductions in frontal–subcortical regions [5, 11]. This is consistent with studies of brain anatomy of children with ADHD, which reported a 5 % reduction in overall cerebral volume [3].
Jin et al. [6] used neuroimaging in medication-naïve ADHD children, and suggests that 20 % to 25 % of neurons in the globus pallidus had died or were severely dysfunctional, and reported a mild hyperactivity of the cholinergic system in the striatum. Other reports implicate reductions in specific areas of the prefrontal cortex, basal ganglia, cerebellum, and corpus callosum [9, 11, 12], some of which are outside the frontal–subcortical circuits, but are involved in coordinating activities of multiple brain regions.
3 Mild Abnormalities of Anatomy and Activity
This hypothesis also fits a curious pattern observed in follow-up studies of premature infants by Krägeloh-Mann et al. [7]: A 5 year follow up of a cohort of babies born prematurely and had MRI performed at time of birth found a correlation between later incidence of ADHD-like symptoms and more mild abnormalities in the neonate MRI. Damage to a frontal–subcortical network important for coordinating motivation and cognition in decision-making processes, like learning from mistakes and delaying gratification to maximize short- and long-term benefits of choices [1] may lead ADHD sufferers to have dysfunctional responses to reward and punishment [2], including severe delay aversion [10].
Functional MRI studies have found frontal hypoactivity affecting the anterior cingulate, dorsolateral, and inferior prefrontal cortex, portions of parietal cortex, basal ganglia, and thalamus [4]. Recent studies have shown disruptions in ADHD affect not only the activity in these brain regions, but also the way in which they connect with one another to form networks [11].
Acronyms
- ADHD
- attention-deficit/hyperactivity disorder
- DA
- dopamine
References
[1] A. Bechara. The role of emotion in decision-making: evidence from neurological patients with orbitofrontal damage. Brain Cogn, 55(1):30–40, Jun 2004. doi: 10.1016/j.bandc.2003.04.001.
[2] L. C. Bidwell, F. J. McClernon, and S. H. Kollins. Cognitive enhancers for the treatment of adhd. Pharmacol Biochem Behav, 99(2): 262–74, Aug 2011. doi: 10.1016/j.pbb.2011.05.002.
[3] F. X. Castellanos, P. P. Lee, W. Sharp, N. O. Jeffries, D. K. Greenstein, L. S. Clasen, J. D. Blumenthal, R. S. James, C. L. Ebens, J. M. Walter, A. Zijdenbos, A. C. Evans, J. N. Giedd, and J. L. Rapoport. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA, 288(14):1740–8, Oct 2002.
[4] S. G. Dickstein, K. Bannon, F. X. Castellanos, and M. P. Milham. The neural correlates of attention deficit hyperactivity disorder: an ale meta-analysis. J Child Psychol Psychiatry, 47(10):1051–62, Oct 2006. doi: 10.1111/j.1469-_7610.2006.01671.x.
[5] S. V. Faraone, T. Spencer, M. Aleardi, C. Pagano, and J. Biederman. Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol, 24(1): 24–9, Feb 2004. doi: 10.1097/01.jcp.0000108984.11879.95.
[6] Z. Jin, Y. Zang, Y. Zeng, L. Zhang, and Y. Wang. Striatal neuronal loss or dysfunction and choline rise in children with attention-deficit hyperactivity disorder: a 1H-magnetic resonance spectroscopy study. Neuroscience letters, 315(1):45–48, 2001.
[7] I. Krägeloh-Mann, P. Toft, J. Lunding, J. Andresen, O. Pryds, and H. C. Lou. Brain lesions in preterms: origin, consequences and compensation. Acta Paediatr, 88(8):897–908, Aug 1999.
[8] H. C. Lou. Etiology and pathogenesis of attention-deficit hyperactivity disorder (adhd): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy. Acta Paediatr, 85(11):1266–71, Nov 1996.
[9] L. J. Seidman, E. M. Valera, and G. Bush. Brain function and structure in adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am, 27(2):323–47, Jun 2004. doi: 10.1016/j.psc.2004.01.002.
[10] E. J. Sonuga-Barke, E. Taylor, S. Sembi, and J. Smith. Hyperactivity and delay aversion–i. the effect of delay on choice. J Child Psychol Psychiatry, 33(2):387–98, Feb 1992.
[11] J. Swanson, R. D. Baler, and N. D. Volkow. Understanding the effects of stimulant medications on cognition in individuals with attention-deficit hyperactivity disorder: a decade of progress. Neuropsychopharmacology, 36 (1):207–26, Jan 2011. doi: 10.1038/npp.2010.160.
[12] J. M. Swanson, B. J. Casey, J. Nigg, F. X. Castellanos, N. D. Volkow, and E. Taylor. Clinical and cognitive definitions of attention deficits in children with attention-deficit/hyperactivity disorder. In M. I. Posner, editor, Cognitive neuroscience of attention, pages 430– 445. Guilford, New York, NY, 2004.
[13] J. M. Swanson, M. Kinsbourne, J. Nigg, B. Lanphear, G. A. Stefanatos, N. Volkow, E. Taylor, B. J. Casey, F. X. Castellanos, and P. D. Wadhwa. Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev, 17(1):39–59, Mar 2007. doi: 10.1007/s11065-_007-_9019-_9.
[14] J. J. Volpe. Brain injury in the premature infant–from pathogenesis to prevention. Brain Dev, 19(8):519–34, Dec 1997.