Basal ganglia microstructure and EEG – a research expedition to the Philippines

Christian Beste

by Prof. Dr. rer. nat. Christian Beste
Cognitive Neurophysiology
Department of Child and Adolescent Psychiatry
Faculty of Medicine
TU Dresden (Germany)

The last years have seen an overwhelming amount of research aiming to disentangle the neural mechanisms underlying goal-directed behavior and cognitive control processes. In that regard, the basal ganglia have attracted much interest. For more than 30 years it is known that the striatum is a very complex neuroanatomical structure and can be subdivided into the ‘matrix’ and the ‘striosomes’. Yet, it has been unclear whether this striatal microstructure is also important to consider for cognitive functions.

Basal ganglia microstructure and EEG 1The problem with investigating this question is that striosomes are small islands of neurons embedded and scattered throughout the larger matrix compartment [1,2] and therefore very difficult to investigate directly. While there are some results using optogenetic methods in rodents, nothing is known about the role of the striosomes for human cognition. So, the primary challenge was to find a way to investigate the role of the striosomes for cognition in humans.

However, there is a very rare disease that is characterized by predominant striosomal neurodegeneration, with the matrix being much less affected in its early disease stages [3]; i.e. X-linked dystonia-parkinsonism (XDP). This disease is endemic to Panay island in the Philippines [4] and no patients are known in Europe. So, the only possibility was to plan an expedition to the Philippines, and Panay island in particular and try to examine XDP patients in this setting to gain insights in the role of the striatal microstructure for cognitive functions and goal-directed behavior in particular.

Together with a group from Lübeck (Prof. Münchau) with which we already have many ongoing projects, we decided to examine patients with XDP at Panay islands and at several hospitals in Metro Manila. This was part of projects funded by the Deutsche Forschungsgemeinschaft (DFG) as parts of the SFB 936 (‘Multi-Site communication in the brain’) and SFB 940 (‘Volition and cognitive control – mechanisms, modulators, dysfunctions’).

However, we were aware that for a neurophysiological investigation no equipment was available at the Philippines (especially at Panay island), so we had to ‘transfer’ an EEG lab to the Philippines. This wouldn’t have been possible without the generous support of Brain Products / MES Forschungssysteme, who agreed to lend two 32-channel EEG BrainAmp amplifiers including PowerPacks and other related hardware equipment for the period of the project in November 2015 and to send it to the Philippines.

Basal ganglia microstructure and EEG 2Arriving at the Philippines we were confronted with a lot of bureaucracy that would have been impossible to solve without the help from our colleagues in Manila. Arriving at Panay island we set up our ‘lab’ in different “rural health units” where we were able to test some of these patients. After returning to Metro Manila we proceeded with data collection at different hospitals.

At the end of 2,5 weeks expedition we were happy to have data from more than 20 of these rare patients taking part in 4 different experiments examining different facets of cognitive control. Throughout the entire data collection we were impressed by the stability of EEG measurements using the hardware, providing good data quality in conditions that did not that much reflect ‘standard laboratory conditions’.

Basal ganglia microstructure and EEG 3The results gathered from these experiments indicate that the basal ganglia striosomes play very specific roles during goal-directed behavior and cognitive control: (i) the striosomal microstructure modulates the processing of conscious and subliminal sources of conflict suggesting that microstructural basal ganglia properties are relevant for cognitive control [5]. (ii) The results underscore the importance of striosomes for cognitive function in humans and suggest that striosomes are relays of error-related behavioral adaptation but not inhibitory control [6]. (iii) Striosomal dysfunction is related to predictive coding deficits leading to a better performance in concomitant perceptual decision-making, probably because predictive coding does not interfere with perceptual decision-making processes. These effects may reflect striatal imbalances between the striosomes and the matrix compartment [7].

References:
[1] Crittenden, J.R., and Graybiel, A.M. (2011). Basal Ganglia disorders associated with imbalances in the striatal striosome and matrix compartments. Front. Neuroanat. 5, 59.
[2] Martin, L.J., Blackstone, C.D., Huganir, R.L., and Price, D.L. (1993). The striatal mosaic in primates: striosomes and matrix are differentially enriched in ionotropic glutamate receptor subunits. J. Neurosci. Off. J. Soc. Neurosci. 13, 782–792.
[3] Goto, S., Lee, L.V., Munoz, E.L., Tooyama, I., Tamiya, G., Makino, S., Ando, S., Dantes, M.B., Yamada, K., Matsumoto, S., et al. (2005). Functional anatomy of the basal ganglia in X-linked recessive dystonia-parkinsonism. Ann. Neurol. 58, 7–17.
[4] Lee, L.V., Maranon, E., Demaisip, C., Peralta, O., Borres-Icasiano, R., Arancillo, J., Rivera, C., Munoz, E., Tan, K., and Reyes, M.T. (2002). The natural history of sex-linked recessive dystonia parkinsonism of Panay, Philippines (XDP). Parkinsonism Relat. Disord. 9, 29–38.
[5] Beste, C., Mückschel, M., Rosales, R., Domingo, A., Lee, L., Ng, A., Klein, C., and Münchau, A. (2017). The Basal Ganglia Striosomes Affect the Modulation of Conflicts by Subliminal Information-Evidence from X-Linked Dystonia Parkinsonism. Cereb. Cortex N. Y. N 1991, 1–10.
[6] Beste, C., Mückschel, M., Rosales, R., Domingo, A., Lee, L., Ng, A., Klein, C., and Münchau, A. (2017). Striosomal dysfunction affects behavioral adaptation but not impulsivity-Evidence from X-linked dystonia-parkinsonism. Mov. Disord. Off. J. Mov. Disord. Soc. 32, 576–584.
[7] Beste, C., Mückschel, M., Rosales, R., Domingo, A., Lee, L., Ng, A., Klein, C., and Münchau, A. (2017). Dysfunctions in striatal microstructure can enhance perceptual decision making through deficits in predictive coding. Brain Struct. Funct.

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