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Anatomical location of the frontopontine fibers in the internal capsule in the human brain: a diffusion tensor tractography study Sung Ho Janga, Pyung-Hun Changb, Yeung Ki Kimc and Jeong Pyo Seoa The frontopontine fibers (FPFs) originate from the frontal lobe and end in the pontine nuclei. Many neuroanatomy textbooks have described the FPFs as descending through the anterior limb of the internal capsule. However, several studies have reported controversial results. In this study, using diffusion tensor tractography, we investigated the anatomical location of the FPFs in the internal capsule in the human brain. We recruited 53 healthy volunteers for this study. For reconstruction of the FPFs, the seed region of interest was given in the medial cerebral peduncle of the reconstructed corticospinal tract. The target regions of interest were placed in the three cerebral cortices, respectively: Brodmann’s area (BA) BA 6, BA 8, and BA 9. The anatomical locations of the FPFs were evaluated using the highest probabilistic location in the internal capsule. We measured the relative distance of the FPFs from the middle point at the genu of the internal capsule to the most posterior point of the lenticular nucleus. The relative mean distances of the highest probabilistic location for the FPFs from BA 9, 8, and 6 were 18.18, 32.08, and 43.83% from the middle point

of the genu of the internal capsule, respectively. By contrast, the highest probabilistic location for the corticospinal tract was 74.18%. According to our findings, the FPFs were located at the anterior half of the posterior limb in the internal capsule, in the following order, from the anterior direction: the FPFs from BA 9, BA 8, and BA c 2014 Wolters Kluwer Health 6. NeuroReport 25:117–121  | Lippincott Williams & Wilkins.

Introduction

By contrast, diffusion tensor tractography (DTT), derived from diffusion tensor imaging (DTI), now allows for visualization of the architecture of neural tracts in three dimensions in the live human brain [2,9–11]. Although DTT has the advantage of localization of the FPFs, little is known about the anatomical location of the FPFs [8].

The corticopontine tract is a neural tract extending from the cerebral cortex to the pontine nuclei [1]. It can be classified as the frontopontine fibers (FPFs), parietopontine fibers, temporopontine fibers, and occipitopontine fibers, according to the cerebral origin. The FPFs originate from the frontal lobe and end in the pontine nuclei. The internal capsule is an important structure for the passage of many neural tracts from the cerebral cortex to the brainstem and thalamus. Because the internal capsule is a very narrow area, compared with the whole cerebral cortex, this area is known to be related to poor outcome in terms of motor function [2]. Many neuroanatomy textbooks have described the FPFs as descending through the anterior limb of the internal capsule. However, several studies have reported controversial results: the anterior limb or the posterior limb of the internal capsule [3–8]. In research on the anatomical location of the FPFs in the human brain, previous studies have employed dye tracing of the degenerated fiber tracts or confocal laser and polarized light microscopy in the post-mortem brain [3,5,6]. Brain CT has also been used for localization of the FPFs in patients with intracerebral hemorrhage [4]. However, these evaluation methods could not identify and visualize neural tracts in the live human brain. c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0959-4965 

NeuroReport 2014, 25:117–121 Keywords: anatomy, diffusion tensor tractography, frontopontine fibers, internal capsule a Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Gyeongsan, Republic of Korea, bDepartment of Robotics Engineering, Graduate School, Daegu Gyeongbuk Institute of Science & Technology and cDepartment of Physical Medicine and Rehabilitation, Leaders Rehabilitation Center, Daegu, Republic of Korea

Correspondence to Jeong Pyo Seo, MS, Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Taegu 705-717, Republic of Korea Tel: + 82 53 620 4098; fax: + 82 53 620 3508; e-mail: [email protected] Received 21 August 2013 accepted 4 October 2013

In the current study, using DTT, we investigated the anatomical location of the FPFs in the internal capsule in the human brain.

Participants and methods Participants

Fifty-three right-handed healthy individuals (males: 28, females: 25, mean age: 34.1 years; range: 20–58 years) with no previous history of psychiatric, neurological, or physical illness were enrolled in this study. The Edinburgh Handedness Inventory was used for evaluation of handedness [12]. All participants understood the purpose of the study and provided written, informed consent before participation. The study protocol was approved by the Institutional Review Board of a university hospital. Data acquisition

DTI data were obtained using a Synergy-L SENSE head coil on a 1.5T Gyroscan Intera system (Philips, Best, DOI: 10.1097/WNR.0000000000000076

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118 NeuroReport 2014, Vol 25 No 2

the Netherlands) equipped with single-shot echo-planar imaging. For each of the 32 noncollinear diffusionsensitizing gradients, we acquired 67 contiguous slices parallel to the anterior commissure–posterior commissure line. Imaging parameters were as follows: acquisition matrix = 96  96, reconstructed to matrix = 128  128 matrix, field of view = 221  221 mm2, TR = 10 726 ms, TE = 76 ms, parallel imaging reduction factor (SENSE factor) = 2, EPI factor = 49 and b = 1000 s/mm2, NEX = 1, slice gap = 0 mm, and slice thickness = 2.3 mm (acquired voxel size 1.73  1.73  2.3 mm3). Fiber tracking

The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library was used for analysis of diffusion-weighted imaging data. Affine multiscale two-dimensional registration was used for correction of head motion effect and image distortion due to eddy current. A probabilistic tractography method based on a multifiber model was used for fiber tracking, and applied in the current study utilizing tractography routines implemented in FMRIB Diffusion (0.5 mm step lengths, 5000 streamline samples, curvature thresholds = 0.2) [13–15]. For analysis of the corticospinal tract (CST), the seed region of interest (ROI) was placed on the lower pons (anterior blue portion on the color map) and the target ROI was placed on the primary motor cortex [Brodmann’s area (BA) 4]. For reconstruction of the FPFs, the seed ROI was given in the medial cerebral peduncle of the reconstructed CST. The target ROIs were placed in the three cerebral cortices, respectively: BA 6, BA 8, and BA 9 [16]. Boundaries of BA 4, BA 6, BA 8, and BA 9 were set as follows: (a) BA 4 – the anterior boundary: the precentral sulcus, the posterior boundary: the central sulcus, the medial boundary: the midline between the right and left hemisphere, and the lateral boundary: the lateral sulcus. (b) BA 6 – the anterior boundary: the line drawn through the anterior commissure perpendicular to the anterior commissure–posterior commissure line, the posterior boundary: the precentral sulcus, the medial boundary: the midline between the right and left hemisphere, and the lateral boundary: the lateral sulcus. (c) BA 8 – the anterior boundary: the second bank of the dorsolateral prefrontal cortex from the precentral sulcus, the posterior boundary: the anterior margin of BA 6, the medial boundary: the midline between the right and left hemisphere, and the lateral boundary: the inferior frontal sulcus. (d) BA 9 – the anterior boundary: the anterior edge of the axial slice, the posterior boundary: anterior margin of BA 8, the medial boundary: the midline between the right and left hemisphere, and the lateral boundary: the inferior frontal sulcus (Fig. 1a) [16]. Measurements of the anatomical locations of the frontopontine fibers at the posterior limb

The locations of the FPFs and CST were defined as the highest probabilistic location at the posterior limb of

the internal capsule on the color map of the axial slice: 6.9 mm above the anterior commissure–posterior commissure line. The highest probability location, which indicates the most probable location of the reconstructed FPFs and CST, was calculated by highest connection point among the generated 5000 sample streamlines. As shown in Fig. 1, we defined line a (the middle point at the genu of the internal capsule) and line b (the most posterior point of the lenticular nucleus). We measured the distance between line a and line b, and then between line a and the highest probability point of each of the three FPFs and the CST as pixel units. Locations were calculated in pixel units and then converted to millimeters (1 pixel = 1.73  1.73 mm). We calculated the relative anteroposterior distance of the three FPFs and CST using the following equation:

Anteroposteriordistanceð % Þ ¼ Distance between line a and highest probability point 100: Distance between line a and line b Statistical analysis

SPSS software (v.15.0; SPSS Inc., Chicago, Illinois, USA) was used for data analysis. The highest probabilistic location was used for performance of one-way analysis of variance with Fisher’s LSD (least significant difference) post-hoc test for determination of variances between each of the three FPFs and the CST, respectively. The independent t-test was used for determination of the difference between the right and left hemisphere. The level of significance was set to P less than 0.05.

Results We reconstructed the three different FPFs (the reconstruction ratio: 100%), which originated from BA 9, 8, and 6, in 106 cerebral hemispheres of 53 healthy participants. All of the reconstructed FPFs passed through the posterior limb of the internal capsule and all of the highest probabilistic locations for each FPF were located anterior to the CST. Table 1 shows the mean distances of the highest probabilistic locations of each FPF from the middle point of the genu of the internal capsule. The relative mean distances of the highest probabilistic location for the FPFs from BA 9, 8, and 6 were 18.18, 32.08, and 43.83% from the middle point for the genu of the internal capsule, respectively. By contrast, the highest probabilistic location for the CST was 74.18%. The highest probabilistic locations of the three FPFs and the CST differed significantly (P < 0.05). However, no significant differences were observed between the right and left hemisphere (P > 0.05).

Discussion Several previous studies have reported on the anatomical location of the FPFs in the human brain [3–8]. In 1950, Beck [3] demonstrated the anatomical location of the

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Anatomical location of the FPFs Jang et al. 119

Fig. 1

(a)

Seed ROI

(b)

Target ROI FPF ROI

CST

R

A

R

(c)

a

b

R

Yellow : BA9

Pink : BA8

Green : BA6

Red : BA4

(a) The seed region of interest (ROI) was given on the low pons [skyblue color – for the corticospinal tract (CST)] and the medial cerebral peduncle of the reconstructed CST [blue color – for the frontopontine fibers (FPFs)]. Target ROIs were placed on Brodmann’s area 9 (BA 9) (yellow red color), BA 8 (pink color), BA 6 (green color), and BA 4 (red color). (b) FPFs and CST were reconstructed in both hemispheres (yellow – FPF from BA 9, pink – FPF from BA 8, green – FPF from BA 6, red – CST). (c) The highest probabilistic location of the FPFs and CST at the posterior limb of the internal capsule (left). Landmarks used to determine the location of the FPFs and CST (line a – passing through the middle point of the genu of the internal capsule, line b – passing through the most posterior point of the lenticular nucleus).

Table 1

Absolute and relative mean distances of the highest probability points of the frontopontine fiber in the posterior limb of the internal

capsule Anterior to posterior distance Right hemisphere (n = 53) FPF from BA mm % FPF from BA mm % FPF from BA mm % Corticospinal mm %

Left hemisphere (n = 53)

P-value Total (n = 106)

0.00* 0.00

9

w

4.18 (±1.42) 18.65 (±6.41)

3.98 (±1.54) 17.72 (±6.77)

4.08 (±1.48) 18.18 (±6.58)

0.00z

7.02 (±1.53) 31.22 (±6.52)

7.41 (±1.84) 32.94 (±7.62)

7.21 (±1.70) 32.08 (±7.11)

0.00}

9.76 (±2.12) 43.57 (±9.64)

9.92 (±1.74) 44.09 (±6.48)

9.84 (±1.93) 43.83 (±8.18)

0.008

16.42 (±1.68) 73.15 (±6.51)

16.88 (±1.69) 75.21 (±6.47)

16.65 (±1.70) 74.18 (±6.54)

0.00z

8

6

tract

Values indicate means (±SDs). Post-hoc least significant difference test was used for comparisons of diffusion tensor image parameters. BA, Brodmann’s area; FPF, frontopontine fiber. *Between FPF from BA 9 and FPF from BA 8. w Between FPF from BA 9 and FPF from BA 6. z Between FPF from BA 9 and corticospinal tract. } Between FPF from BA 8 and FPF from BA 6. 8 Between FPF from BA 8 and corticospinal tract. z Between FPF from BA 6 and corticospinal tract.

prefrontopontine tract by tracing the degenerated fiber tracts using Nissl stain in seven post-mortem human brains after leucotomy. They found that the prefronto-

pontine fibers showed degeneration at the posterior limb of the internal capsule in six of seven patients. In 1990, using brain CT, Tredici et al. [4] reported lesions at the

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120 NeuroReport 2014, Vol 25 No 2

posterior limb in patients with ataxic hemiparesis syndrome following intracerebral hemorrhage in the frontal lobe. In 1999, Axer et al. [5], using a confocal laser and polarized light microscopy, demonstrated that the FPFs occupied 38% of the anterior limb in four postmortem human brains. Subsequently, using the same method, the same research group (2000) reported that the FPFs were intermingled with fibers of the anterior thalamic peduncle in the anterior limb of the internal capsule in four post-mortem human brains [6]. In 2007, Habas and Cabanis [7] demonstrated that the FPFs were descended through the rostral posterior limb of the internal capsule in four healthy individuals. A recent DTT study (2011) using probabilistic tractography in 14 healthy human brains reported that the corticopontocerebellar tract, which originated from the primary sensorimotor cortex, descended through the posterior limb of the internal capsule [8]. In the current study, we investigated the anatomical location of the FPFs in the internal capsule. According to our findings, the FPFs were located at the anterior half of the posterior limb in the internal capsule, in the following order, from the anterior direction: the FPFs from BA 9, BA 8, and BA 6. In contrast, the CST, which originated from BA 4, was located in the posterior half of the posterior limb in the internal capsule. Regarding the anatomical location of the CST, the CST is known to be located in the posterior portion of the posterior limb [17–20]. According to previous studies, it seems certain that the frontothalamic fibers pass through the anterior limb of the internal capsule; however, the anatomical location of the FPFs has been controversial [3–8,21,22]. Among previous studies, two studies using a confocal laser and polarized light microscopy for analysis of the tract location as the angle of neural tracts only in the internal capsule reported that the FPFs were located in the anterior limb of the internal capsule [5,6]. By contrast, studies analyzing the whole brain using post-mortem pathology or DTT have reported that the FPFs were located in the posterior limb [3,4,7,8]. In the current study, we used DTT for elucidation of the anatomical location of the FPFs in the live human brain; consequently, the results of this study coincide with two previous DTT studies [7,8].

be considered. First, the fiber tracking technique of DTI is operator-dependent. Second, DTI may underestimate or overestimate the neural fiber tracts. Third, regions of fiber complexity and crossing can prevent full reflection of the underlying fiber architecture [23,24]. Fourth, the DTI characteristics of FPFs could be influenced by individual experience and learning [25].

Acknowledgements This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A4A01001873). Conflicts of interest

There are no conflicts of interest.

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Conclusion We found that the FPFs were located in the anterior half of the posterior limb in the human brain. To the best of our knowledge, this is the first study using DTT to investigate the anatomical location of the FPFs according to the cerebral origin in the internal capsule. This information would be valuable for clinicians in the field of neuroscience in the effort to achieve a thorough understanding of the neurological manifestations, and in prediction of the clinical outcome, and for establishment of therapeutic strategies for treatment of patients with brain injury. However, the limitations of DTI should

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Anatomical location of the frontopontine fibers in the internal capsule in the human brain: a diffusion tensor tractography study.

The frontopontine fibers (FPFs) originate from the frontal lobe and end in the pontine nuclei. Many neuroanatomy textbooks have described the FPFs as ...
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