Memory Modulation Factors in Hippocampus Exposed to Radiation
Although the key scene of the hippocampus in memory processes is obvious, the specificity of its participation in information processing is far from being established. Current advanced neuroimaging enables to operate with precise morphometric parameters.
The aim of the study was to reveal fine memory rearrangements under mechanical impact on the hippocampus by a neoplasm and radiation exposure in the course of therapy.
Materials and Methods. We used a homogeneous sample of 28 patients with parasellar meningiomas adjacent to hippocampus. In 10 patients (5 with left-sided and 5 with right-sided meningiomas), the tumor was located near the hippocampus but exhibited no mechanical effect on it. In 18 patients (10 with left-sided and 8 with right-sided tumors), the neoplasm compressed the adjacent hippocampus. The control group consisted of 39 healthy subjects. All three groups were comparable in age, education, and gender characteristics. In order to control tumor growth, the patients underwent radiotherapy when the hippocampus involuntary was exposed to a dose comparable to that in the tumor (30 sessions with a single focal dose of 1.8 Gy, total dose — 54.0 Gy).
Based on the literature data on hippocampus involved in mnestic processes, a special methodology to investigate memory was developed. Incorrect responses the subjects made when identifying previously memorized images were classified as neutralizing the novelty factor of an identified stimulus or as wrongly emphasizing its novelty.
Results. At the first observation point (before radiation therapy) all groups underwent a complete standardized neuropsychological examination and performed a battery of cognitive tests. The overall results of the tests assessing attention, memory, thinking processes, and neurodynamic indicators corresponded to standard values. A mild brain compression by the tumor without brain tissue destruction was not accompanied by focal neuropsychological symptoms and deficit manifestations in the cognitive sphere. However, as early as in the first observation point, the number of “pattern separation” errors in the clinical group was significantly higher than that in healthy subjects.
The second observation point (immediately after radiotherapy) and the third observation point — 6 months after the treatment — showed that, in general, the patients’ cognitive sphere condition was not deteriorating, and in a number of parameters was characterized by positive dynamics, apparently associated with some tumor reduction due to the therapy provided. However, the distribution of errors in the original method significantly changed. When previously memorized stimuli were recognized, the errors neutralizing the novelty factor of the evaluated stimulus increased, while the number of errors with overestimating the stimuli novelty decreased.
All tendencies hypothetically (according to the published data) associated with the changes in functional activity of the hippocampus were more pronounced in the subgroup of patients with mechanical impact of the tumor on hippocampus.
Conclusion. The continuous flow of impressions any person has at any moment of his activity is most likely marked by the hippocampus in a continuum “old–similar–new”. The present study has shown that mechanical impact on the hippocampus combined with radiation exposure changes the range of assessments towards the prevailing labeling “old, previously seen, already known”.
- Scoville W.B., Milner B. Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 1957; 20(1): 11–21, https://doi.org/10.1136/jnnp.20.1.11.
- Buklina S.B. Narusheniya vysshikh psikhicheskikh funktsiy pri porazhenii glubinnykh i stvolovykh struktur mozga [Violations of higher mental functions with damage to the deep and stem structures of the brain]. Moscow: MEDpress-inform; 2016.
- Vinogradova O.S. Gippokamp i pamyat’ [Hippocampus and memory]. Moscow: Nauka; 1975.
- Yassa M.A., Stark C.E.L. Pattern separation in the hippocampus. Trends Neurosci 2011; 34(10): 515–525, https://doi.org/10.1016/j.tins.2011.06.006.
- Encinas J.M., Michurina T.V., Peunova N., Park J.H., Fishell G., Koulakov A., Enikolopov G. Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 2011; 8(5): 566–579, https://doi.org/10.1016/j.stem.2011.03.010.
- Tolentino J.C., Pirogovsky E., Luu T., Toner C.K., Gilbert P.E. The effect of interference on temporal order memory for random and fixed sequences in nondemented older adults. Learn Mem 2012; 19(6): 251–255, https://doi.org/10.1101/lm.026062.112.
- Fountain D.M., Soon W.C., Matys T., Guilfoyle M.R., Kirollos R., Santarius T. Volumetric growth rates of meningioma and its correlation with histological diagnosis and clinical outcome: a systematic review. Acta Neurochir (Wien) 2017; 159(3): 435–445, https://doi.org/10.1007/s00701-016-3071-2.
- Alekseeva A., Enikolopova E., Krotkova O., Danilov G., Galkin M. Dynamics of cognitive functions in patients with parasellar meningiomas undergoing radiotherapy. In: The Fifth International Luria Memorial Congress “Lurian Approach in International Psychological Science”. Glozman J., Vindeker O. (editors). Netherlands: KnE Life Sciences; 2018; p. 42–48, https://doi.org/10.18502/kls.v4i8.3261.
- Rogers L., Barani I., Chamberlain M., Kaley T.J., McDermott M., Raizer J., Schiff D., Weber D.C., Wen P.Y., Vogelbaum M.A. Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review. J Neurosurg 2015; 122(1): 4–23, https://doi.org/10.3171/2014.7.jns131644.
- Chera B.S., Amdur R.J., Patel P., Mendenhall W.M. A radiation oncologist’s guide to contouring the hippocampus. Am J Clin Oncol 2009; 32(1): 20–22, https://doi.org/10.1097/coc.0b013e318178e4e8.
- Luriya A.R. Vysshie korkovye funktsii cheloveka i ikh narusheniya pri lokal’nykh porazheniyakh mozga [Human higher cortical functions and their disorders in local brain lesions]. Moscow: Izdatel’stvo MGU; 1969; 504 p.
- Balentova S., Adamkov M. Molecular, cellular and functional effects of radiation-induced brain injury: a review. Int J Mol Sci 2015; 16(11): 27796–27815, https://doi.org/10.3390/ijms161126068.
- Makale M.T., McDonald C.R., Hattangadi-Gluth J., Kesari S. Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours. Nat Rev Neurol 2017; 13(1): 52–64, https://doi.org/10.1038/nrneurol.2016.185.
- Stevenson R.F., Reagh Z.M., Chun A.P., Murray E.A., Yassa M.A. Pattern separation and source memory engage distinct hippocampal and neocortical regions during retrieval. J Neurosci 2020; 40(4): 843–851, https://doi.org/10.1523/jneurosci.0564-19.2019.
- Velichkovsky B.M., Krotkova O.A., Kotov A.A., Orlov V.A., Verkhlyutov V.M., Ushakov V.L., Sharaev M.G. Consciousness in a multilevel architecture: evidence from the right side of the brain. Conscious Cogn 2018; 64: 227–239, https://doi.org/10.1016/j.concog.2018.06.004.
- Quian Quiroga R. No pattern separation in the human hippocampus. Trends Cogn Sci 2020; 24(12): 994–1007, https://doi.org/10.1016/j.tics.2020.09.012.
- Li Q., Tavakol S., Royer J., Larivière S., Vos De Wael R., Park B., Paquola C., Zeng D., Caldairou B., Bassett D.S., Bernasconi A., Bernasconi N., Frauscher B., Smallwood J., Caciagli L., Li S., Bernhardt B.C. Human brain function during pattern separation follows hippocampal and neocortical connectivity gradients. bioRxiv 2020, https://doi.org/10.1101/2020.06.22.165290.
- Zheng J., Stevenson R.F., Mander B.A., Mnatsakanyan L., Hsu F.P.K., Vadera S., Knight R.T., Yassa M.A., Lin J.J. Multiplexing of theta and alpha rhythms in the amygdala-hippocampal circuit supports pattern separation of emotional information. Neuron 2019; 102(4): 887-898.e5, https://doi.org/10.1016/j.neuron.2019.03.025.
- Riphagen J.M., Schmiedek L., Gronenschild E.H.B.M., Yassa M.A., Priovoulos N., Sack A.T., Verhey F.R.J., Jacobs H.I.L. Associations between pattern separation and hippocampal subfield structure and function vary along the lifespan: a 7 T imaging study. Sci Rep 2020; 10(1): 7572, https://doi.org/10.1038/s41598-020-64595-z.