Acta Neurologica Belgica
https://doi.org/10.1007/s13760-019-01077-8

LETTER TO THE EDITOR

Injury of the prefronto-caudate tract in a patient with apathy
following intracerebral hemorrhage in the caudate nucleus
Sung Ho Jang1 · Seong Ho Kim2 · Hyeok Gyu Kwon3
Received: 5 December 2018 / Accepted: 7 January 2019
© Belgian Neurological Society 2019

Introduction
The caudate nucleus (CN), as a part of the basal ganglia,
interconnects with the prefrontal cortex (PFC), temporal cortex, frontal eye field, and cerebellum. These connections are
involved in motor and cognitive functions [1]. Specifically, the
prefronto-caudate tract is involved in apathy, anxiety, depression, and disinhibition [2]. Apathy is classically defined as a
lack of feeling, emotion, interest and concern, and clinically
presents as the absence of motivation, voluntary movement
or speech [3]. Injury of the CN, PFC, or the prefronto-caudate
tract in particular, connected to the medial PFC, and orbitofrontal cortex (OFC) is related to apathy [4, 5].
Diffusion tensor tractography (DTT), a three-dimensional
imaging tool, is based on diffusion tensor imaging (DTI).
This technique measures characteristics of water diffusion in
brain tissue, allowing assessment of the state of neural connectivity [6]. Probabilistic DTT, that reflects the distribution
of underlying fiber structure, is widely used for researching
the neural connectivity of neural structures in the human
brain. Several studies have investigated the prefronto-basal
ganglia circuit including the prefronto-caudate tract in
patients with schizophrenia, attention-deficit/hyperactivity
* Hyeok Gyu Kwon
khg0715@hanmail.net
Sung Ho Jang
strokerehab@hanmail.net
Seong Ho Kim
shkim@medical.yeungnam.ac.kr
1

Department of Physical Medicine and Rehabilitation,
College of Medicine, Yeungnam University, Gyeongsan,
Republic of Korea

2

Department of Neurosurgery, College of Medicine,
Yeungnam University, Gyeongsan, Republic of Korea

3

Department of Physical Therapy, College of Health
Sciences, Catholic University of Pusan, 57 Oryundae‑ro,
Geumjeong‑gu, Pusan 46252, Republic of Korea

disorder, and major depressive disorder [7–10]. However,
little is known on this topic in patients with intracerebral
hemorrhage (ICH).
In this study, we report on a patient with apathy in whom
injury of the prefronto-caudate tract was detected on DTT
following ICH in the caudate nucleus.

Case report
A 55-year-old male underwent extraventricular drainage
(both prefrontal approaches) for intraventricular hemorrhage at the neurology department of a university hospital
(Fig. 1a). A brain CT at that time also showed ICH in the
right CN (Fig. 1a). At 8 months after the drainage procedure,
he was admitted to the rehabilitation department of the same
university hospital because he was not significantly recovering cognition and gait despite rehabilitation at a local rehabilitation hospital beginning 3 weeks after the drainage. The
patient showed severe apathy (Apathy Scale score: 21 [full
score: 42]). Brain MR images taken at 8 months after the ICH
showed leukomalactic lesions in the right CN (Fig. 1b). The
patient’s daughter provided signed, informed consent, and
our institutional review board approved the study protocol.
DTI data were acquired at 9 months after the ICH using
a six-channel head coil on a 1.5 T (Philips, Ltd., Best, the
Netherlands) with 32 gradients. Imaging parameters were
as follows: acquisition matrix = 96 × 96, reconstructed to
matrix = 192 × 192, field of view = 240 × 240 ­mm2, repetition time = 10,398 ms, echo time = 72 ms, b = 1000 s/mm2,
and a slice thickness of 2.5 mm. Head motion effect and
image distortion due to eddy current were corrected by affine
multi-scale two-dimensional registration. Fiber tracking was
performed with the Oxford Centre for Functional Magnetic
Resonance Imaging of the Brain Diffusion Software with the
default tractography option. For analysis of the CN, the seed
region of interest was given at the CN that was isolated using
adjacent structures (medial boundary: the lateral ventricle;

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Fig. 1  a Brain CT at onset shows intracerebral hemorrhage in the
right caudate nucleus (CN) (red arrow). b Brain MRI shows leukomalactic lesion in the right CN (blue arrow) at 8 months after onset. c

The neural connectivity of the CN to the prefrontal cortex including
the medial prefrontal cortex and orbitofrontal cortex is decreased in
the right hemisphere. (Color figure online)

lateral boundary: the anterior limb of the internal capsule).
The threshold of 10 streamlines was applied for the results of
fiber tracking.
The neural connectivity of the CN to the PFC including the
medial PFC (Brodmann area [BA]: 10 and 12) and OFC (BA:
11 and 13) was decreased in the right hemisphere (Fig. 1c).

to the medial PFC and OFC was injured in the right hemisphere (lesion side). We believed that ICH on the CN was
attributed to injury of the prefronto-caudate tract (medial
PFC) and contributed to the patient’s apathy. Many studies report lesions on the CN in patients with apathy using
conventional CT or MRI [2, 4, 5, 11–14,, 4, 5, 11–14].
Bathia and Marsden reported that 28% of patients with
a CN lesion lacked initiative and voluntary behavior [5].
In 1997, Bokura and Robinson found that 6 of 21 patients
with a CN lesion showed a lack of motivation [13]. These
studies were compatible with our results. Thus, our results
suggest the importance of evaluation for the connectivity
of the CN to the PFC in patients with apathy following
ICH in the CN.

Discussion
In the current study, injury of the prefronto-caudate
tract in a patient with apathy following ICH in a caudate
nucleus was demonstrated by DTT. We found injury of the
prefronto-caudate tract. In detail, connectivity of the CN

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Acta Neurologica Belgica

Using DTT, a few studies have reported on injury of
the prefronto-caudate tract in patients with schizophrenia,
attention-deficit/hyperactivity disorder, and major depressive disorder [7–10]. Only one DTT study has reported on
apathy associated with injury of the prefronto-caudate tract
in a patient with mild traumatic brain injury [15]. In 2017,
Jang and Kwon demonstrated that aggravation of apathy
in a patient was associated with worsening injury of the
prefronto-caudate tract particularly medial PFC and OFC
in both hemispheres following mild traumatic brain injury
using follow-up DTTs [15]. To the best of our knowledge,
this is the first study to prove injury of the prefronto-caudate
tract in patients with ICH. However, the limitations of this
study should be considered. First, because it is a case report,
this study is limited. Second, we could not examine associations between the severity of apathy and injury of the
prefronto-caudate tract. Third, probabilistic DTT can produce both false-positive and -negative results due to multiple
fiber orientations in a voxel. Therefore, we suggest further
studies involving large numbers of patients and overcoming
the limitations of DTT.
In conclusion, injury of the prefronto-caudate tract in a
patient who developed severe apathy following ICH was
demonstrated by DTT. We believe that analysis of the prefronto-caudate tract using DTT would be useful in understanding the causes of apathy after ICH.
Acknowledgements This work was supported by the National Research
Foundation of Korea (NRF) grant funded by the Korean Government
(MSIP) (No. 2018R1A2B6000996).

Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical standard The authors declare that they acted in accordance
with ethical standards laid down in the 1964 Declaration of Helsinki.
Informed consent Informed consent was obtained from all individual
participants included in the study.

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