Neuroscience Letters 559 (2014) 72–75
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Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Neural connectivity of the anterior body of the fornix in the human brain: Diffusion tensor imaging study Sung Ho Jang, Hyeok Gyu Kwon ∗ Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Republic of Korea
h i g h l i g h t s • We investigated the neural connectivity of the anterior body of fornix. • The fornix, part of the Papez circuit, plays a role in episodic memory. • Anterior body of fornix connected to the cholinergic nuclei and memory function area.
a r t i c l e
i n f o
Article history: Received 24 September 2013 Received in revised form 20 November 2013 Accepted 21 November 2013 Keywords: Fornix Diffusion tensor imaging Neural connectivity Anterior commissure
a b s t r a c t A few studies have reported on the neural connectivity of the fornix in the human brain, however, little is known about the neural connectivity of the anterior body of the fornix. In this study, we used diffusion tensor imaging in investigation of the neural connectivity of the anterior body of the fornix in normal subjects. Forty healthy subjects were recruited for this study. A seed region of interest was placed on the anterior body of the fornix using the FMRIB Software Library. Connectivity was defined as the incidence of connection between the anterior body of the fornix and any neural structure of the brain at the threshold of 5, 25, and 50 streamlines. In all subjects, the anterior body of the fornix showed 100% connectivity to the anterior commissure and hypothalamus at thresholds of 5, 25, and 50. On the other hand, regarding the thresholds of 5, 25, and 50, the anterior body of the fornix showed connectivity to the septal forebrain region (53.8, 23.8, and 15.0%), frontal lobe via anterior commissure (41.3,12.5, and 10.0%), medial temporal lobe (85.0,66.3, and 62.5%), lateral temporal lobe (75.0, 56.3, and 35.0%), occipital lobe (21.3, 5.0, and 1.3%), frontal lobe via septum pellucidum (28.8, 13.8, and 8.8%), tegmentum of midbrain (7.5, 5.0, and 0%), tectum of midbrain (2.5,0, and 0%), and tegmentum of pons (5.0,0, and 0%). The anterior body of the fornix showed high connectivity with the anterior commissure and hypothalamus, and brain areas relevant to cholinergic nuclei (the septal forebrain region and brainstem) and memory function (the medial temporal lobe). © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction The fornix is involved in the transfer of information on episodic memory as a part of the Papez circuit between the hippocampus and the mammillary body [5,7,15,18]. Unmasking of latent neural connection is one of the recovery mechanisms after brain injury; therefore, elucidation of the neural connectivity of a neural structure is important in terms of neural control in the normal brain, and brain plasticity in patients with brain injury [1,2]. The fornix is located adjacent to important neural structures such as the anterior
∗ Corresponding author. Tel.: +82 53 620 4098; fax: +82 53 625 3508. E-mail addresses: [email protected] (S.H. Jang), [email protected] (H.G. Kwon). 0304-3940/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neulet.2013.11.040
commissure and corpus callosum, however, neural connectivity of the fornix has been neglected [8]. That is because research on neural connectivity of the fornix has been difficult using conventional brain CT or MRI [6,16]. Diffusion tensor imaging (DTI) can evaluate white matter, and enables three-dimensional visualization and estimation of the fornix [9,11,14,17]. As a result, a few studies have reported on the neural connectivity of the posterior body of the fornix in the normal brain, and unusual neural connectivity of the anterior and posterior bodies of the fornix in patients with brain injury [8,21,22]. However, no study on neural connectivity of the anterior body of the fornix in the normal human brain has been reported. In the current study, we used DTI in investigation of the neural connectivity of the anterior body of the fornix in normal subjects.
S.H. Jang, H.G. Kwon / Neuroscience Letters 559 (2014) 72–75
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2. Methods 2.1. Subjects Forty healthy subjects (males: 22, females: 18, mean age: 31.8 years, range: 20–50 years) with no previous history of neurological, physical, or psychiatric illness were recruited. All subjects understood the purpose of the study and provided written, informed consent prior to participation. The study protocol was approved by the institutional review board of the Yeungnam university hospital. 2.2. Data acquisition DTI data were acquired using a 6-channel head coil on a 1.5 T Philips Gyroscan Intera (Philips, Ltd., Best, The Netherlands) with single-shot echo-planar imaging. For each of the 32 non-collinear diffusion sensitizing 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; field of view = 221 × 221 mm2 ; TR = 10, 726 ms; TE = 76 ms; parallel imaging reduction factor = 2 (SENSE factor); EPI factor = 59; b = 1000 s/mm2 ; NEX = 1; and a slice thickness of 2.3 mm (acquired voxel size 1.73 × 1.73 × 2.3 mm3 ). 2.3. Probabilistic fiber tracking Analysis of diffusion-weighted imaging data was performed using the Oxford Centre for functional magnetic resonance imaging of the brain (FMRIB) software library (FSL; www.fmrib.ox.ac.uk/fsl). Head motion effect and image distortion due to eddy current were corrected by affine multi-scale two-dimensional registration. Fiber tracking was performed using a probabilistic tractography method based on a multi-fiber model, and applied in the current study utilizing tractography routines implemented in FMRIB Diffusion (5000 streamline samples, 0.5 mm step lengths, curvature thresholds = 0.2) [3,4,13]. We used the two regions of interest (ROIs) in order to elucidate the connectivity of the anterior body of the fornix. The first ROI was drawn on the anterior body of the fornix (green color) as a seed mask on the color map with the coronal image. The second ROI was placed on the junction between the body and crus as an exclusion mask on the color map with the coronal image [5]. Out of 5000 samples generated from a seed voxel, results were visualized at the threshold of 5, 25, and 50 streamlines through each voxel for analysis. Connectivity was defined as the incidence of connection between the anterior body of the fornix and any neural structure of the brain. 3. Results A summary of the connectivity of the anterior body of the fornix is shown in Table 1. In all subjects, the anterior body of the fornix showed 100% connectivity to the anterior commissure and hypothalamus at thresholds of 5, 25, and 50 (Fig. 1). On the other hand, the anterior body of the fornix was found to be connected to other brain regions via three neural structures: (1) the anterior commissure–to the septal forebrain regions, frontal lobe, medial temporal lobe, lateral temporal lobe, and occipital lobe, (2) the septum pellucidum–to the frontal lobe, and (3) the dorsal longitudinal fasciculus–to the brainstem. Regarding the thresholds of 5, 25, and 50, the anterior body of the fornix showed connectivity to the septal forebrain region (53.8, 23.8, and 15.0%), frontal lobe via anterior commissure (41.3, 12.5, and 10.0%), medial temporal lobe (85.0, 66.3, and 62.5%), lateral temporal lobe (75.0, 56.3, and 35.0%), occipital lobe (21.3, 5.0, and 1.3%), frontal lobe via septum pellucidum (28.8, 13.8, and 8.8%), tegmentum of midbrain (7.5, 5.0,
Fig. 1. (A) Neural connectivity of the anterior body of the fornix at a threshold of 5, 25, and 50. (B) Diffusion tensor tractography results regarding connectivity between the anterior body of the fornix and each brain area: the septum pellucidum (brokenlined arrow), the anterior commissure (dotted-lined arrow and dotted circle), the hypothalamus (long broken-lined arrow), the body of the fornix (lined arrow), the dorsal longitudinal fasciculus (broken-dotted-lined arrow), the frontal lobe (greenlined quadrangle)–the anterior body of the fornix connected with the frontal lobe via the anterior commissure and the septum pellucidum, the temporal lobe (skybluelined quadrangle)–the anterior body of the fornix connected with the temporal lobe via the anterior commissure and the occipital lobe (yellow-lined quadrangle)–the anterior body of the fornix connected with the occipital lobe via the anterior commissure.
and 0%), tectum of midbrain (2.5, 0, and 0%), and tegmentum of pons (5.0, 0, and 0%). 4. Discussion In the current study, we investigated neural connectivity of the anterior body of the fornix in the normal human brain, using probabilistic tracking. We found the following characteristics of connectivity of the anterior body of the fornix: (1) all subjects showed connectivity with the anterior commissure and the hypothalamus irrespective of thresholds, (2) the anterior body of the fornix showed connectivity with areas known to contain cholinergic neurons: the septal forebrain region and the brainstem, although we could not completely clarify the connectivity to the cholinergic nuclei, and (3) high connectivity to the medial temporal lobe, which contains important structures for memory function, including the hippocampus and the entorhinal cortex. The fornix is known to be connected to the septal region via the precommissural fornix anteriorly, the mammillary body via the postcommissural fornix anteriorly, and hippocampus via the crus of the fornix posteriorly [5,23]. However, several recent studies using diffusion tensor tractography (DTT) have reported unusual or unknown neural connections of the fornix that had not been previously reported in normal subjects and patients with brain injury [8,21,22]. In 2013, Yeo and Jang reported on a patient who showed an unusual neural connection of an injured fornix following traumatic axonal injury of both fornical crus [21]. In the right fornix, an abnormal neural tract originating from the right crus passed
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S.H. Jang, H.G. Kwon / Neuroscience Letters 559 (2014) 72–75
Table 1 Incidence of connectivity between the anterior body of the fornix and brain regions. Passage areas
Anterior commissure
Septum pellucidum Dorsal longitudinal fasciculus
Target areas
Threshold 5 (%)
Threshold 25 (%)
Threshold 50 (%)
Anterior commissure Hypothalamus Septal forebrain region Frontal lobe Medial temporal lobe Lateral temporal lobe Occipital lobe Frontal lobe Midbrain-tegmentum Midbrain-tectum Pons-tegmentum
100 100 53.8 41.3 85.0 75.0 21.3 28.8 7.5 2.5 5.0
100 100 23.8 12.5 66.3 56.3 5.0 13.8 5.0 0.0 0.0
100 100 15.0 10.0 62.5 35.0 1.3 8.8 0.0 0.0 0.0
Connectivity (%)
through the splenium of the corpus callosum and then connected with the right inferior longitudinal fasciculus. By contrast, in the left fornix, another abnormal neural tract originating from the left column of the fornix connected with the left medial temporal lobe and the splenium of the corpus callosum via the anterior commissure. These findings were not observed in normal control subjects, therefore, it was suggested that these abnormal neural tracts of the fornix were the result of neural reorganization triggered by bilateral injury of the fornical crus. The abnormal neural tract originating from the left fornical column connected with the left medial temporal lobe via the anterior commissure appears to coincide with the result of this study. Subsequently, the same authors reported on a patient with subarachnoid hemorrhage due to rupture of an anterior communicating cerebral artery aneurysm [22]. The proximal portion of both fornical crus showed discontinuations on six-week and sevenmonth DTTs; however, seven-month DTT showed that the end of the right fornical body was connected with the splenium of the corpus callosum and then branched to the right medial temporal lobe and right thalamus. Although this patient showed severe cognitive impairment at six weeks after onset, her cognition showed continuous improvement with time; consequently, her cognition was within normal range at seven months after onset. Therefore, the unusual neural connection between the injured fornical body, and the medial temporal lobe was suggested to be a recovery phenomenon of an injured fornix. In a recent study, Kwon and Jang [2013] reported on the neural connectivity of the posterior body of the fornix in normal subjects [8]. Results of this study showed that the posterior body of the fornix had connectivity with brain regions that had not been reported previously, including the cerebral cortex, the brainstem, and the splenium of the corpus callosum in normal subjects. To the best of our knowledge, this is the first study using DTI to demonstrate neural connectivity of the anterior body of the fornix in normal subjects. In conclusion, according to our findings, the anterior body of the fornix had high connectivity to the anterior commissure and hypothalamus, and brain areas relevant to cholinergic nuclei (the septal forebrain region and brainstem) and memory function (the medial temporal lobe). We think that the results of this study would be helpful in investigation of the neural network associated with memory and recovery mechanisms following fornical injury in patients with brain injury. However, limitations of DTI should be considered [10,12,19,20]. DTI is a powerful anatomic imaging tool, which can demonstrate gross fiber architecture; however, due to crossing fiber or partial volume effect, DTI can produce both false positive and negative results throughout the white matter of the brain [10,20]. In particular, probabilistic fiber tracking can cause false fiber trajectory. Therefore, conduct of further studies using other DTI analysis programs should be encouraged. In addition, studies for clinical application of our results for patients with brain injury are also invited.
Acknowledgements This research was supported byBasic Science Research theNational Research Foundation of Programthrough Korea(NRF)funded by theMinistry of Education, Science and Technology(2012R1A1A4A01001873) References [1] P. Bach-y-Rita, Brain plasticity as a basis of the development of rehabilitation procedures for hemiplegia, Scand. J. Rehabil. Med. 13 (1981) 73–83. [2] P. Bach-y-Rita, Central nervous system lesions: sprouting and unmasking in rehabilitation, Arch. Phys. Med. Rehabil. 62 (1981) 413–417. [3] T.E. Behrens, H.J. Berg, S. Jbabdi, M.F. Rushworth, M.W. Woolrich, Probabilistic diffusion tractography with multiple fibre orientations: what can we gain? Neuroimage 34 (2007) 144–155. [4] T.E. Behrens, H. Johansen-Berg, M.W. Woolrich, S.M. Smith, C.A. WheelerKingshott, P.A. Boulby, G.J. Barker, E.L. Sillery, K. Sheehan, O. Ciccarelli, A.J. Thompson, J.M. Brady, P.M. Matthews, Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging, Nat. Neurosci. 6 (2003) 750–757. [5] L. Concha, D.W. Gross, C. Beaulieu, Diffusion tensor tractography of the limbic system, Am. J. Neuroradiol. 26 (2005) 2267–2274. [6] E.A. Gaffan, D. Gaffan, J.R. Hodges, Amnesia following damage to the left fornix and to other sites. A comparative study, Brain 114 (Pt 3) (1991) 1297–1313. [7] J.H. Hong, B.Y. Choi, C.H. Chang, S.H. Kim, Y.J. Jung, W.M. Byun, S.H. Jang, Injuries of the cingulum and fornix after rupture of an anterior communicating artery aneurysm: a diffusion tensor tractography study, Neurosurgery 70 (2012) 819–823. [8] S.H. Jang, H.G. Kwon, Neural connectivity of the posterior body of the fornix in the human brain: diffusion tensor imaging study, Neurosci. Lett. 549 (2013) 116–119. [9] N. Kunimatsu, S. Aoki, A. Kunimatsu, O. Abe, H. Yamada, Y. Masutani, K. Kasai, H. Yamasue, K. Ohtomo, Tract-specific analysis of white matter integrity disruption in schizophrenia, Psychiatry Res. 201 (2012) 136–143. [10] S.K. Lee, D.I. Kim, J. Kim, D.J. Kim, H.D. Kim, D.S. Kim, S. Mori, Diffusion-tensor MR imaging and fiber tractography: a new method of describing aberrant fiber connections in developmental CNS anomalies, Radiographics 25 (2005) 53–65, discussion 66-58. [11] N. Nakayama, A. Okumura, J. Shinoda, Y.T. Yasokawa, K. Miwa, S.I. Yoshimura, T. Iwama, Evidence for white matter disruption in traumatic brain injury without macroscopic lesions, J. Neurol. Neurosurg. Psychiatry 77 (2006) 850–855. [12] G.J. Parker, D.C. Alexander, Probabilistic anatomical connectivity derived from the microscopic persistent angular structure of cerebral tissue, Philos. Trans. R. Soc. Lond. B Biol. Sci. 360 (2005) 893–902. [13] S.M. Smith, M. Jenkinson, M.W. Woolrich, C.F. Beckmann, T.E. Behrens, H. Johansen-Berg, P.R. Bannister, M. De Luca, I. Drobnjak, D.E. Flitney, R.K. Niazy, J. Saunders, J. Vickers, Y. Zhang, N. De Stefano, J.M. Brady, P.M. Matthews, Advances in functional and structural MR image analysis and implementation as FSL, Neuroimage 23 (Suppl. 1) (2004) S208–S219. [14] K. Sugiyama, T. Kondo, S. Higano, M. Endo, H. Watanabe, K. Shindo, S. Izumi, Diffusion tensor imaging fiber tractography for evaluating diffuse axonal injury, Brain Inj. 21 (2007) 413–419. [15] A.G. Thomas, P. Koumellis, R.A. Dineen, The fornix in health and disease: an imaging review, Radiographics 31 (2011) 1107–1121. [16] D.M. Tucker, D.P. Roeltgen, R. Tully, J. Hartmann, C. Boxell, Memory dysfunction following unilateral transection of the fornix: a hippocampal disconnection syndrome, Cortex 24 (1988) 465–472. [17] J.Y. Wang, K. Bakhadirov, M.D. Devous Sr., H. Abdi, R. McColl, C. Moore, C.D. Marquez de la Plata, K. Ding, A. Whittemore, E. Babcock, T. Rickbeil, J. Dobervich, D. Kroll, B. Dao, N. Mohindra, C.J. Madden, R. Diaz-Arrastia, Diffusion tensor tractography of traumatic diffuse axonal injury, Arch. Neurol. 65 (2008) 619–626.
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[21] S.S. Yeo, S.H. Jang, Neural reorganization following bilateral injury of the fornix crus in a patient with traumatic brain injury, J. Rehabil. Med. 45 (2013) 595–598. [22] S.S. Yeo, S.H. Jang, Recovery of an injured fornix in a stroke patient, J. Rehabil. Med. 45 (2013) 1078–1080. [23] S.S. Yeo, J.P. Seo, Y.H. Kwon, S.H. Jang, Precommissural fornix in the human brain: a diffusion tensor tractography study, Yonsei Med. J. 54 (2013) 315–320.
Contents lists available at ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Neural connectivity of the anterior body of the fornix in the human brain: Diffusion tensor imaging study Sung Ho Jang, Hyeok Gyu Kwon ∗ Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Republic of Korea
h i g h l i g h t s • We investigated the neural connectivity of the anterior body of fornix. • The fornix, part of the Papez circuit, plays a role in episodic memory. • Anterior body of fornix connected to the cholinergic nuclei and memory function area.
a r t i c l e
i n f o
Article history: Received 24 September 2013 Received in revised form 20 November 2013 Accepted 21 November 2013 Keywords: Fornix Diffusion tensor imaging Neural connectivity Anterior commissure
a b s t r a c t A few studies have reported on the neural connectivity of the fornix in the human brain, however, little is known about the neural connectivity of the anterior body of the fornix. In this study, we used diffusion tensor imaging in investigation of the neural connectivity of the anterior body of the fornix in normal subjects. Forty healthy subjects were recruited for this study. A seed region of interest was placed on the anterior body of the fornix using the FMRIB Software Library. Connectivity was defined as the incidence of connection between the anterior body of the fornix and any neural structure of the brain at the threshold of 5, 25, and 50 streamlines. In all subjects, the anterior body of the fornix showed 100% connectivity to the anterior commissure and hypothalamus at thresholds of 5, 25, and 50. On the other hand, regarding the thresholds of 5, 25, and 50, the anterior body of the fornix showed connectivity to the septal forebrain region (53.8, 23.8, and 15.0%), frontal lobe via anterior commissure (41.3,12.5, and 10.0%), medial temporal lobe (85.0,66.3, and 62.5%), lateral temporal lobe (75.0, 56.3, and 35.0%), occipital lobe (21.3, 5.0, and 1.3%), frontal lobe via septum pellucidum (28.8, 13.8, and 8.8%), tegmentum of midbrain (7.5, 5.0, and 0%), tectum of midbrain (2.5,0, and 0%), and tegmentum of pons (5.0,0, and 0%). The anterior body of the fornix showed high connectivity with the anterior commissure and hypothalamus, and brain areas relevant to cholinergic nuclei (the septal forebrain region and brainstem) and memory function (the medial temporal lobe). © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction The fornix is involved in the transfer of information on episodic memory as a part of the Papez circuit between the hippocampus and the mammillary body [5,7,15,18]. Unmasking of latent neural connection is one of the recovery mechanisms after brain injury; therefore, elucidation of the neural connectivity of a neural structure is important in terms of neural control in the normal brain, and brain plasticity in patients with brain injury [1,2]. The fornix is located adjacent to important neural structures such as the anterior
∗ Corresponding author. Tel.: +82 53 620 4098; fax: +82 53 625 3508. E-mail addresses: [email protected] (S.H. Jang), [email protected] (H.G. Kwon). 0304-3940/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neulet.2013.11.040
commissure and corpus callosum, however, neural connectivity of the fornix has been neglected [8]. That is because research on neural connectivity of the fornix has been difficult using conventional brain CT or MRI [6,16]. Diffusion tensor imaging (DTI) can evaluate white matter, and enables three-dimensional visualization and estimation of the fornix [9,11,14,17]. As a result, a few studies have reported on the neural connectivity of the posterior body of the fornix in the normal brain, and unusual neural connectivity of the anterior and posterior bodies of the fornix in patients with brain injury [8,21,22]. However, no study on neural connectivity of the anterior body of the fornix in the normal human brain has been reported. In the current study, we used DTI in investigation of the neural connectivity of the anterior body of the fornix in normal subjects.
S.H. Jang, H.G. Kwon / Neuroscience Letters 559 (2014) 72–75
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2. Methods 2.1. Subjects Forty healthy subjects (males: 22, females: 18, mean age: 31.8 years, range: 20–50 years) with no previous history of neurological, physical, or psychiatric illness were recruited. All subjects understood the purpose of the study and provided written, informed consent prior to participation. The study protocol was approved by the institutional review board of the Yeungnam university hospital. 2.2. Data acquisition DTI data were acquired using a 6-channel head coil on a 1.5 T Philips Gyroscan Intera (Philips, Ltd., Best, The Netherlands) with single-shot echo-planar imaging. For each of the 32 non-collinear diffusion sensitizing 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; field of view = 221 × 221 mm2 ; TR = 10, 726 ms; TE = 76 ms; parallel imaging reduction factor = 2 (SENSE factor); EPI factor = 59; b = 1000 s/mm2 ; NEX = 1; and a slice thickness of 2.3 mm (acquired voxel size 1.73 × 1.73 × 2.3 mm3 ). 2.3. Probabilistic fiber tracking Analysis of diffusion-weighted imaging data was performed using the Oxford Centre for functional magnetic resonance imaging of the brain (FMRIB) software library (FSL; www.fmrib.ox.ac.uk/fsl). Head motion effect and image distortion due to eddy current were corrected by affine multi-scale two-dimensional registration. Fiber tracking was performed using a probabilistic tractography method based on a multi-fiber model, and applied in the current study utilizing tractography routines implemented in FMRIB Diffusion (5000 streamline samples, 0.5 mm step lengths, curvature thresholds = 0.2) [3,4,13]. We used the two regions of interest (ROIs) in order to elucidate the connectivity of the anterior body of the fornix. The first ROI was drawn on the anterior body of the fornix (green color) as a seed mask on the color map with the coronal image. The second ROI was placed on the junction between the body and crus as an exclusion mask on the color map with the coronal image [5]. Out of 5000 samples generated from a seed voxel, results were visualized at the threshold of 5, 25, and 50 streamlines through each voxel for analysis. Connectivity was defined as the incidence of connection between the anterior body of the fornix and any neural structure of the brain. 3. Results A summary of the connectivity of the anterior body of the fornix is shown in Table 1. In all subjects, the anterior body of the fornix showed 100% connectivity to the anterior commissure and hypothalamus at thresholds of 5, 25, and 50 (Fig. 1). On the other hand, the anterior body of the fornix was found to be connected to other brain regions via three neural structures: (1) the anterior commissure–to the septal forebrain regions, frontal lobe, medial temporal lobe, lateral temporal lobe, and occipital lobe, (2) the septum pellucidum–to the frontal lobe, and (3) the dorsal longitudinal fasciculus–to the brainstem. Regarding the thresholds of 5, 25, and 50, the anterior body of the fornix showed connectivity to the septal forebrain region (53.8, 23.8, and 15.0%), frontal lobe via anterior commissure (41.3, 12.5, and 10.0%), medial temporal lobe (85.0, 66.3, and 62.5%), lateral temporal lobe (75.0, 56.3, and 35.0%), occipital lobe (21.3, 5.0, and 1.3%), frontal lobe via septum pellucidum (28.8, 13.8, and 8.8%), tegmentum of midbrain (7.5, 5.0,
Fig. 1. (A) Neural connectivity of the anterior body of the fornix at a threshold of 5, 25, and 50. (B) Diffusion tensor tractography results regarding connectivity between the anterior body of the fornix and each brain area: the septum pellucidum (brokenlined arrow), the anterior commissure (dotted-lined arrow and dotted circle), the hypothalamus (long broken-lined arrow), the body of the fornix (lined arrow), the dorsal longitudinal fasciculus (broken-dotted-lined arrow), the frontal lobe (greenlined quadrangle)–the anterior body of the fornix connected with the frontal lobe via the anterior commissure and the septum pellucidum, the temporal lobe (skybluelined quadrangle)–the anterior body of the fornix connected with the temporal lobe via the anterior commissure and the occipital lobe (yellow-lined quadrangle)–the anterior body of the fornix connected with the occipital lobe via the anterior commissure.
and 0%), tectum of midbrain (2.5, 0, and 0%), and tegmentum of pons (5.0, 0, and 0%). 4. Discussion In the current study, we investigated neural connectivity of the anterior body of the fornix in the normal human brain, using probabilistic tracking. We found the following characteristics of connectivity of the anterior body of the fornix: (1) all subjects showed connectivity with the anterior commissure and the hypothalamus irrespective of thresholds, (2) the anterior body of the fornix showed connectivity with areas known to contain cholinergic neurons: the septal forebrain region and the brainstem, although we could not completely clarify the connectivity to the cholinergic nuclei, and (3) high connectivity to the medial temporal lobe, which contains important structures for memory function, including the hippocampus and the entorhinal cortex. The fornix is known to be connected to the septal region via the precommissural fornix anteriorly, the mammillary body via the postcommissural fornix anteriorly, and hippocampus via the crus of the fornix posteriorly [5,23]. However, several recent studies using diffusion tensor tractography (DTT) have reported unusual or unknown neural connections of the fornix that had not been previously reported in normal subjects and patients with brain injury [8,21,22]. In 2013, Yeo and Jang reported on a patient who showed an unusual neural connection of an injured fornix following traumatic axonal injury of both fornical crus [21]. In the right fornix, an abnormal neural tract originating from the right crus passed
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S.H. Jang, H.G. Kwon / Neuroscience Letters 559 (2014) 72–75
Table 1 Incidence of connectivity between the anterior body of the fornix and brain regions. Passage areas
Anterior commissure
Septum pellucidum Dorsal longitudinal fasciculus
Target areas
Threshold 5 (%)
Threshold 25 (%)
Threshold 50 (%)
Anterior commissure Hypothalamus Septal forebrain region Frontal lobe Medial temporal lobe Lateral temporal lobe Occipital lobe Frontal lobe Midbrain-tegmentum Midbrain-tectum Pons-tegmentum
100 100 53.8 41.3 85.0 75.0 21.3 28.8 7.5 2.5 5.0
100 100 23.8 12.5 66.3 56.3 5.0 13.8 5.0 0.0 0.0
100 100 15.0 10.0 62.5 35.0 1.3 8.8 0.0 0.0 0.0
Connectivity (%)
through the splenium of the corpus callosum and then connected with the right inferior longitudinal fasciculus. By contrast, in the left fornix, another abnormal neural tract originating from the left column of the fornix connected with the left medial temporal lobe and the splenium of the corpus callosum via the anterior commissure. These findings were not observed in normal control subjects, therefore, it was suggested that these abnormal neural tracts of the fornix were the result of neural reorganization triggered by bilateral injury of the fornical crus. The abnormal neural tract originating from the left fornical column connected with the left medial temporal lobe via the anterior commissure appears to coincide with the result of this study. Subsequently, the same authors reported on a patient with subarachnoid hemorrhage due to rupture of an anterior communicating cerebral artery aneurysm [22]. The proximal portion of both fornical crus showed discontinuations on six-week and sevenmonth DTTs; however, seven-month DTT showed that the end of the right fornical body was connected with the splenium of the corpus callosum and then branched to the right medial temporal lobe and right thalamus. Although this patient showed severe cognitive impairment at six weeks after onset, her cognition showed continuous improvement with time; consequently, her cognition was within normal range at seven months after onset. Therefore, the unusual neural connection between the injured fornical body, and the medial temporal lobe was suggested to be a recovery phenomenon of an injured fornix. In a recent study, Kwon and Jang [2013] reported on the neural connectivity of the posterior body of the fornix in normal subjects [8]. Results of this study showed that the posterior body of the fornix had connectivity with brain regions that had not been reported previously, including the cerebral cortex, the brainstem, and the splenium of the corpus callosum in normal subjects. To the best of our knowledge, this is the first study using DTI to demonstrate neural connectivity of the anterior body of the fornix in normal subjects. In conclusion, according to our findings, the anterior body of the fornix had high connectivity to the anterior commissure and hypothalamus, and brain areas relevant to cholinergic nuclei (the septal forebrain region and brainstem) and memory function (the medial temporal lobe). We think that the results of this study would be helpful in investigation of the neural network associated with memory and recovery mechanisms following fornical injury in patients with brain injury. However, limitations of DTI should be considered [10,12,19,20]. DTI is a powerful anatomic imaging tool, which can demonstrate gross fiber architecture; however, due to crossing fiber or partial volume effect, DTI can produce both false positive and negative results throughout the white matter of the brain [10,20]. In particular, probabilistic fiber tracking can cause false fiber trajectory. Therefore, conduct of further studies using other DTI analysis programs should be encouraged. In addition, studies for clinical application of our results for patients with brain injury are also invited.
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