Severe Apathy Due to Injury of Prefronto-caudate Tract

Abstract The caudate nucleus, which is vulnerable to hypoxic–ischemic brain injury (HI-BI), is important to cognitive function because it is connected to the prefrontal cortex. Using diffusion tensor tractography (DTT), no study on injury of the prefronto-caudate tract in a patient with HI-BI has been reported so far. Here, we report a patient with severe apathy who showed injury of the prefronto-caudate tract following HI-BI, which was demonstrated by DTT. A 38-year-old female patient suffered HI-BI induced by carbon monoxide poisoning following attempted suicide for a period of approximately four hours. From the onset, the patient showed severe apathy (7 months after onset-the Apathy Scale score was 24 [full score: 42]). Brain MR images taken at seven months after onset showed no abnormality. On 7-month DTT, the neural connectivity of the caudate nucleus to the medial prefrontal cortex (Brodmann area: 10 and 12) and orbitofrontal cortex (Brodmann area: 11 and 13) was decreased in both hemispheres. Using DTT, injury of the prefronto-caudate tract was demonstrated in a patient who showed severe apathy following HI-BI. We believe that injury of the prefronto-caudate tract might be a pathogenetic mechanism of apathy in patients with HI-BI.


Introduction
Hypoxic-ischemic brain injury (HI-BI), caused by insufficient oxygen supply to the brain because of various etiologies including cardiopulmonary arrest, respiratory failure, or carbon monoxide poisoning, affects various brain regions [1]. In particular, several specific brain regions including the basal ganglia, hippocampus, cerebellum, and thalamic nuclei are known to be vulnerable to HI-BI [2]. Among these vulnerable brain regions, the caudate nucleus (CN), a part of the basal ganglia, is important for cognitive function by connecting to the prefrontal cortex. Thus, the prefrontocaudate tract which is known to be related to apathy, anxiety, depression, and disinhibition, might be vulnerable to HI-BI [3]. In particular, injury of the prefronto-caudate tract, which is connected to the medial prefrontal cortex (PFC), is associated with apathy [4].
Diffusion tensor tractography (DTT) derived from diffusion tensor imaging (DTI) has an advantage in estimating and visualizing the connectivity of the CN to the PFC and enables detection of subtle or invisible neural injury by detection of characteristics of water diffusion [5]. In particular, probabilistic DTT, which considers the distribution of underlying fiber structure, has been widely used for investigation of the neural connectivity of neural structures in the human brain [5]. As a result, several studies have investigated the frontostriatal tract including the prefrontocaudate tract in patients with obsessivecompulsive disorder, bipolar mood disorder, attention-deficit/hyperactivity disorder, and schizophrenia [6]. However, no study using DTT to investigate injury of the prefronto-caudate tract in patients with HI-BI has been reported so far. We hypothesized that DTT could demonstrate injury of the prefronto-caudate tract in a patient who showed severe apathy even though conventional brain MRI did not reveal any specific brain lesion.
In this study, we report a patient who showed injury of the prefronto-caudate tract following HI-BI, which was demonstrated by DTT. 10mg) Brain MR images taken at seven months after onset showed no abnormality ( Fig.1-A).

Discussion
In the current study, we investigated the neural connectivity of the CN in a patient with HI-BI using DTT and found that the neural connectivity of the CN to the medial PFC (BA 10 and 12) and orbitofrontal cortex (BA 11 and 13) was decreased in both hemispheres. In conclusion, using DTT, injury of the prefronto-caudate tract was demonstrated in a patient who showed severe apathy following HI-BI. We believe that injury of the prefrontocaudate tract might be a pathogenetic mechanism of apathy in patients with HI-BI.
It should be noted that this study is limited because it is based on a case report. When using DTT, both false positive and negative results can occur throughout the white matter of the brain because of complex fiber configurations such as crossing or kissing fibers and partial volume effects. Therefore, we suggest further studies involving larger numbers of patients be conducted to overcome the limitations of DTI.