When Agatha Christie’s famous Belgian detective, Hercule Poirot, attributed his investigative success to “the little grey cells”—components of the brain’s grey matter—he may well have been correct. He usually was.
Today, neuroscientists delving into the comparatively neglected “other half of the brain” are defining the highly important roles of white matter. They’ve found that in patients with heroin-use disorder, white matter is involved in the recovery of brain structure and function after long-term abstinence.
Those reports have led neuroscientists to investigate the characteristics of recovery in brain function, with an eye toward improving available treatments. The neuroscientists include the authors of a study, discussed below, recently published in the Journal of Addiction Medicine.
To investigate the characteristics of white matter in patients with heroin use disorder during short and long abstinence, the team used a sophisticated type of noninvasive magnetic resonance imaging (MRI) known as quantitative diffusion tensor imaging (quantitative DTI). This tool enables scientists to see white matter and evaluate its structure.
What Is White Matter, and Do We Care?
White matter is one of the two major components of the brain, the other being the grey matter—home of Hercule Poirot’s “little grey cells.”
In fact, most of the brain’s cells reside in the grey matter. In the white matter, networks of nerve cell extensions branch extensively and connect with key areas in the grey matter. Without this connectivity, the brain couldn’t function.
And heroin, in long-term use, is known to cause abnormalities in the structure and function of white matter.
So, yes, we do care about white matter.
Contains most of the brain’s nerve cell bodies
Includes areas involved in muscle control and sensory perception—hearing and seeing—also memory, decision-making
Consists largely of the nerve cell extensions known as axons, and their covering, the myelin sheath*
Axons along with dendrites in the grey matter act as connections linking the brain’s four lobes and its center of emotions
*Dendrites, as well as axons, are nerve cell extensions, but they lack a myelin sheath, which is white, and thus are in the grey matter
Components and Functions of Nerve Cells
A nerve cell (neuron) consists of a cell body and its extensions—one axon, in humans, up to three feet in length; and one or more dendrites.
The cell body:
- Receives information from other nerve cells, carried to it via one or more dendrites
- Sends information to other nerve cells, via one axon
A myelin sheath, wrapped around each axon, protects the axon, confines the nerve impulse to the axon, and speeds the transmission of electrical impulses.
The cells in the grey matter cannot function without the network of connections in the white matter—connections that allow communication between areas of the brain and other parts of the body.
Authors’ Expectations for the Study
In the current study, the authors planned to explore the characteristics and integrity of the white matter of patients who had heroin use disorder and who were in short-term or long-term abstinence. The idea was to identify the relationship between length of abstinence from heroin and integrity of the white matter, using the sophisticated imaging tool mentioned earlier, quantitative DTI.
The authors speculated that white matter integrity would be reduced in former patients compared to normal controls. They postulated that the reduced integrity would be related to damage to the myelin sheath, or to axon compromise, or both, and that the white matter would gradually recover when the patient was no longer using heroin.
The study group, all males, included 17 patients in long-tern abstinence (heroin-free for about 24 weeks), 19 in short-term abstinence (about 2 weeks), and 20 healthy controls. Pre-study treatment had consisted of psychological rehabilitation and vocational training; no medication.
The study found that connectivity in extensive regions in the white matter was significantly reduced in patients with short-term abstinence, but in only two clusters in patients with long-term abstinence.
The authors listed the following major findings:
- Patients with heroin use disorder showed extensive white matter impairment, compared with healthy controls
- White matter integrity in most regions was restored after long-term abstinence, mainly in the myelin sheath
- Restoration of white matter integrity correlated significantly with the length of abstinence
The authors commented that the findings “suggested that the time-dependent recovery of white matter, especially the restoration of the myelin sheath,” occurred in patients with long-term abstinence, and that “longer-abstinent duration with strategies of enhancing myelination may improve treatment effectiveness.
In the Discussion section, the authors looked at the body of work in this area, and offered this reassuring comment:
“There is increasing evidence to suggest that the impaired brain function and structure of HUD patients can be restored after long-term abstinence.”
But some questions remain.
Although other studies have shown results similar to those reported here, is it possible that former heroin users are at high risk of relapse, even after prolonged abstinence, due to “rewiring” within the white matter?
A National Institutes of Health news release dated March 21, 2019 suggests this is the case. “Opioid use causes a surge of the neurotransmitter dopamine in the brain, and habitual use ‘rewires’ the brain’s reward system,” possibly generating irresistible cravings for opioids and susceptibility to associated cues.
The authors of the current study point out that other studies have found “lasting impairments” in the function of key areas of the brain during the first 18 months of abstinence. These results are consistent with those in their own study, indicating that damage to the myelin sheath may persist for a long time.
The authors also note the possibility of heroin relapse:
Prolonged structural and functional alterations in some brain regions may be related to an ongoing cognitive deficit and may put [patients with heroin use disorder] at risk of heroin relapse and other risky behaviors. Therefore, the duration of this impairment in [white matter] and its relationship with functional and cognitive deficits need to be determined in further research.
Also needed, say the authors, are more effective treatments. For example, ways of enhancing, acquiring, or replacing the myelin sheath is an unexplored area that could be developed into a new treatment strategy.
Zhu J, Yan X, Lyu Z, et al. Characteristics of White Matter Integrity During Different Phases of Abstinence in Heroin Use Disorders: A Diffusion Tensor Imaging Study. J Addict Med. March 09, 2022. doi: 10.1097/ADM.0000000000000962
For Further Reading
NIH to test experimental drug to curb opioid cravings. News Release. National Institutes of Health. March 21, 2019. Accessed June 11, 2022. https://www.nih.gov/news-events/news-releases/nih-test-experimental-drug-curb-opioid-cravings
Tolomeo S, Steele JD, Ekhtiari H, Baldacchino A. Chronic heroin use disorder and the brain: Current evidence and future implications. Prog Neuropsychopharmacol Biol Psychiatry. 2021;111:110148. doi:10.1016/j.pnpbp.2020.110148
Ieong HF, Yuan Z. Resting-State Neuroimaging and Neuropsychological Findings in Opioid Use Disorder during Abstinence: A Review. Front Hum Neurosci. 2017;11:169. Published 2017 Apr 6. doi:10.3389/fnhum.2017.00169
Wang X, Yu R, Zhou X, et al. Reversible brain white matter microstructure changes in heroin addicts: a longitudinal study. Addict Biol. 2013;18(4):727-728. doi:10.1111/j.1369-1600.2011.00316.x
Li Q, Wang Y, Zhang Y, et al. Assessing cue-induced brain response as a function of abstinence duration in heroin-dependent individuals: an event-related fMRI study. PLoS One. 2013;8(5):e62911. Published 2013 May 7. doi:10.1371/journal.pone.0062911
Biernacki K, McLennan SN, Terrett G, Labuschagne I, Rendell PG. Decision-making ability in current and past users of opiates: A meta-analysis. Neurosci Biobehav Rev. 2016;71:342-351. doi:10.1016/j.neubiorev.2016.09.011
Passetti F, Clark L, Mehta MA, Joyce E, King M. Neuropsychological predictors of clinical outcome in opiate addiction. Drug Alcohol Depend. 2008;94(1-3):82-91. doi:10.1016/j.drugalcdep.2007.10.008
Wilson MJ, Vassileva J. Neurocognitive and psychiatric dimensions of hot, but not cool, impulsivity predict HIV sexual risk behaviors among drug users in protracted abstinence. Am J Drug Alcohol Abuse. 2016;42(2):231-241. doi:10.3109/00952990.2015.1121269