Keywords

1 Introduction

The biochemical exchanges between the neurons of our brain take place in the synapses and produce a small electrical activity detectable by the placement of electrodes on the scalp using diagnostic neurophysiological recording techniques such as electroencephalography (EEG) or evoked potentials (EP). In addition, in recent years scientific interest in non-invasive brain stimulation techniques has grown, which, through neuroplasticity, allow the treatment of pathologies such as pain or depression.

The method known as the International 10–20 System was established by Herbert H. Jasper in 1958 [1]. This method, adopted by the International Federation of Clinical Neurophysiology, standardises the placement of 21 EEG electrodes on the scalp. Through some percentages of the circumference (either 10% or 20%, hence the name of the method) and distances between four basic anatomical landmarks, the head is divided into proportional positions to offer adequate coverage of all regions of the brain, thus correlating external locations of the skull with the underlying cortical areas. Therefore, this method has the advantage of considering the variability in the size of the patient's skull, since it uses measurements of the head for the placement of the electrodes. The four anatomical landmarks used to perform the percentage position calculations are the Nasion, the Inion, and the left and right preauricular points.

1.1 Dorsolateral Prefrontal Cortex (DLPFC)

One of the brain regions whose location has been mostly studied by researchers is the dorsolateral prefrontal cortex (DLPFC). The DLPFC is an area in the prefrontal cortex of the primate brain, which is not an anatomical structure, but a functional one, located in the middle frontal gyrus of humans, in the lateral part of the 9 and 46 Brodmann areas (BA). The dorsolateral prefrontal cortex (DLPFC), used for both tDCS and rTMS, has been recognized to be critically involved in cognitive control, including cognitive control over emotions, as well as working memory, cognitive flexibility and planning.

The DLPFC is the most commonly used area of stimulation for the treatment of major depressive disorder (MDD) with rTMS [2, 3], and is also typically used for the relief of certain types of pain [4]. Also, in tDCS, DLPFC localization appears to show a positive therapeutic effect in MDD patients. Moreover, it has been shown to improve performance in various cognitive domains such as executive functions, verbal skills, and memory performance with healthy subjects, but also with patients that suffer Parkinson's disease and have suffered a stroke [5].

The Talairach and Montreal Neurological Institute (MNI) spaces are three-dimensional coordinate systems (also known as “atlases”) of the human brain, used to map the location of brain regions, regardless of individual differences in the size and general shape of the brain. The first MNI template was the MNI305, generated from the average of 305 brain scans, and the current standard MNI template is the ICBM152 (commonly referred to as MNI152), which is the average of 152 normal MRI scans that have been matched to the MNI305 using a 9-parameter affine transform.

1.2 Localization methods for DLPFC

Likewise, it is important to consider that there is significant variability in the anatomy of the head, which interferes with the location of these brain areas. That is why some localization methods consider the morphological variability of the head to better adapt the localization to each subject. The most common methods currently used to localise the DLPFC are neuroimaging and neuronavigation techniques, the “5 cm” method [7, 8], the intl. 10–20 system and the “Beam F3 method” proposed by [4].

The location of the F3 electrode from the 10–20 system is usually used as a target for the DLPFC [4], so many clinical research applications target this location when applying procedures such as TMS to the DLPFC. As this system uses head measurements, thus accounting for variability in head shape, it seems an accurate way to localise the DLPFC. However, for clinicians with little experience with the 10–20 system, the numerous measurements and calculations to locate the F3 position can be time consuming and lead to human errors.

This paper offers a review of the location of the DLPFC zone to understand the problems related to the location of brain areas. Therefore, the main objective is to study the existing methods to locate the dorsolateral prefrontal cortex (DLPFC), analysing the discrepancies shown in the literature when it comes to locating this area of the brain.

2 Methodology

Differences on the MNI152 coordinates appears when the DLPFC location is analysed.

We study these differences and compare the location with the position determined by the International System 10–20 for a realistic MNI152 head model (taking the coordinates of [9] as reference). Studies that provide both coordinates (cerebral and scalp) are used to determine the relationship between the two positions. Based on this information, the brain or scalp positions of the woks that only pointed to one of the two locations are extrapolated. With all the information above, the Euclidean distance d between the MNI positions of the different studies and the reference position can be calculated.

The Brainstorm software [13] is used to visualise the points of the DLPFC, both the scalp and brain coordinates, on a real 3D head model adjusted to the MNI152 atlas.

3 Results

3.1 Coordinates in MNI of the DLPFC

Reviewing the literature, it is observed that in each paper the DLPFC is located in different coordinates. This work focuses on 16 articles that provide the coordinates of the left DLPFC in the MNI Coordinate System [6, 11, 12, 14,15,16,17,18,19,20,21,22,23,24,25,26]. Some articles that are also included provide the coordinates in the Talairach coordinate system, but later studies converted those coordinates to the MNI System. The coordinates provided by Oostenveld as a F3 is used as a gold standard [9]. The coordinates that located the DLPFC in the brain were plotted on the cerebral cortex of the model provided by Brainstorm, while those that located it on the scalp were plotted on the surface of the head volume.

Each of the brain DLPFC locations can be seen in Fig. 1a. However, [18] (light blue in the Fig. 1 legend) is not visible, as it is in the same place as the pink dot representing the BeamF3 location of [26].

The coordinates of the scalp can be seen in Fig. 1b plotted on the surface of the head. In this case, [17] cannot be seen (in red in the legend to Fig. 1b), since it is in the same location as [11]. The same is true of the [18] and the location of [26] from Beam F3 (in light blue and pink in the Fig. 2b legend), which are not seen on the scalp, as they are in the same location as the F3 Oostenveld location (in black) [22].

In addition to the visualisations, Table 1 shows the differences between these positions and the reference ones [9], both for brain and scalp coordinates, respectively. The mean Euclidean distance from the brain coordinates is 11.50 mm (with a SD of 8.02 mm) and for the scalp coordinates the mean is 13.32 mm (with an SD of 8.72 mm).

Fig. 1.
figure 1

Coordinates of the literature represented on the Brainstorm segmentation model. a) Cerebral cortex. b) Cranial volume.

Table 1. MNI Brain coordinates for DLPFC and Euclidean distance errors with respect to the brain gold standard (dB). MNI Scalp coordinates for DLPFC and Euclidean distance errors with respect to the scalp gold standard (ds)

Analysing the brain coordinates, it can be seen that the locations that present the most differences are the coordinates provided by [19] and [26], who used the 5 and 5.5 cm methods. These two locations lie further back in the brain than the rest. On the other hand, the works that located the left DLPFC with greater precision to the Oostenveld F3 cerebral location are primarily [15], who uses the International 10–20 System, followed by [18] and [26]. Note that [18] use a T1-weighted anatomical magnetic resonance imaging scan to locate the position, and MNI coordinates provided by [24] are obtained as an average of 81 points (obtained in different 81 heads). Although the mean value in [24] is close to the actual F3, the results show a high variability (possibly influenced on the morphology of the head). Authors specify that the average Euclidean distance from each individual target to the group average centroid was 9.5 ± 6.1 mm. Its SD is close to the one obtained for the 5.5 cm methods (6.6 mm). The results suggest that neither the Beam F3 nor the 5.5 cm rule are valid methods to precisely locate the same location based on the individual patient's head measurements. A recent study [27] has found that Beam F3 introduces an error that is dependent on the head morphology.

Similar results are obtained with the coordinates of the scalp. Again, the locations obtained with the 5 and 5.5 cm methods place the F3 location too posterior in the scalp, while the works that place the DLPFC more similar to Oostenveld F3 are [15], who found the location with the 10–20 IS, followed by [26] (average of 81 heads) and [18] that use images from magnetic resonances.

4 Conclusions

The comparison of the coordinates in the scientific literature allow us to evaluate the existing localization methods and quantify the differences between them. There is a clear discrepancy between the DLPFC coordinates provided in the literature.

It has been observed that the 5 cm method, or its variants such as the 5.5 cm method, point to a DLPFC site more distant from the one considered correct (errors between 24 and 29 mm). In average, the results of the Beam F3 method are close to the actual F3 position. However, the dispersion of the results raises questions about its feasibility to target the same point for different head morphologies.