Brain Imaging and Behavior DOI 10.1007/s11682-013-9271-y
ORIGINAL RESEARCH
Uncinate fasciculus microstructure and verbal episodic memory in amyotrophic lateral sclerosis: a diffusion tensor imaging and neuropsychological study Foteini Christidi & Ioannis Zalonis & Stavroula Kyriazi & Michalis Rentzos & Efstratios Karavasilis & Elisabeth A. Wilde & Ioannis Evdokimidis
# Springer Science+Business Media New York 2013
Abstract The present study evaluates the integrity of uncinate fasciculus (UF) and the association between UF microstructure and verbal episodic memory (as one of the cognitive functions linked to UF) in non-demented patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). We studied 21 patients with ALS and 11 healthy, demographicallycomparable volunteers. Fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity were the DTI metrics examined. Episodic memory was evaluated with Babcock Story Recall Test and Rey Auditory Verbal Learning Test (RAVLT) for patients; measures of immediate and delayed recall and retention for both tests and sum of words recalled through five learning trials for RAVLT were considered. Patients with ALS showed significant bilateral reduction of axial diffusivity in the UF as compared to controls. Furthermore, there were several significant relations between various DTI metrics (mostly in left hemisphere) and memory measures (specifically for the RAVLT). UF microstructural changes may contribute to ALSrelated memory impairment, with word-list learning performance F. Christidi : M. Rentzos : I. Evdokimidis First Department of Neurology, Aeginition Hospital, Medical School, National and Kapodistrian University, Athens, Greece F. Christidi (*) : I. Zalonis Neuropsychological Laboratory, First Department of Neurology, Aeginition Hospital, Medical School, National and Kapodistrian University, 72-74 Vas. Sophias Avenue, Athens 115 28, Greece e-mail: [email protected] S. Kyriazi : E. Karavasilis Radiology Research Unit, Medical Imaging Department, Evgenidion Hospital, National and Kapodistrian University, Athens, Greece E. A. Wilde Departments of Physical Medicine and Rehabilitation, Neurology and Radiology, Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
relying more upon the integrity of frontal and temporal connections than memory components associated with story recall. Keywords Uncinate fasciculus . Memory function . Diffusion tensor imaging . Amyotrophic lateral sclerosis
Introduction In the past decade, advanced magnetic resonance imaging (MRI) techniques, such as diffusion tensor imaging (DTI), have allowed detection and quantification of sub-clinical motor neuron damage and provided further support for extra-motor involvement in patients with amyotrophic lateral sclerosis (ALS). DTI measures the magnitude and orientation of anisotropic water diffusion in biological tissues and permits the exploration of white matter (WM) pathways in vivo. DTI-derived parameters, such as fractional anisotropy (FA), apparent diffusion coefficient (ADC), and axial and radial diffusivity (DA and DR, respectively) have been deemed proxies for WM integrity (Alexander et al. 2007), and they can be used to evaluate the integrity or disruption of fiber tracts (Mori and Zhang 2006). Regarding extra-motor involvement in ALS, decreased FA values have been reported in the corpus callosum and in WM regions in the frontal and temporal lobes, and increased ADC values have been found in frontal and temporal WM regions (Agosta et al. 2010a; Li et al. 2012; Tsermentseli et al. 2012). The uncinate fasciculus (UF) connects the inferior frontal gyrus and the inferior surfaces of the frontal lobe with the anterior portions of the temporal lobe (Schmahmann et al. 2007). Despite the fact that its role in cognition remains still unclear, there is increasing evidence of its involvement in episodic memory formation and retrieval (Diehl et al. 2008; Fink et al. 2010; Fujie et al. 2008; Nestor et al. 2004; Squire
Brain Imaging and Behavior
and Zola-Morgan 1991). Contrary to the relatively consistent finding of executive dysfunction in patients with ALS (Irwin et al. 2007; Raaphorst et al. 2010), there is variable evidence for deficits in memory functions (Abe et al. 1997; Abrahams et al. 1997; Chari et al. 1996; Dary-Auriol et al. 1997; Frank et al. 1997; Hanagasi et al. 2002; Iwasaki et al. 1990; Kew et al. 1993; Ludolph et al. 1992; Mantovan et al. 2003; Massman et al. 1996; Paulus et al. 2002; Rakowicz and Hodges 1998). Few studies have investigated the nature of memory impairment in these patients; most of them support an encoding or retrieval deficit, mostly related to frontal dysfunction (Mantovan et al. 2003), yet consolidation memory difficulties cannot be excluded (Christidi et al. 2012). In clinical neuropsychological practice, verbal memory is routinely examined through story recall and word-list learning tests, which although initially thought to address interchangeable functions (Delis et al. 1988), are now considered different (Helmstaedter et al. 2009; Randolph et al. 1994; Wicklund et al. 2006). Contrary to the inherent organization of the story recall material, word-list learning tests include either related or unrelated words requiring self-generation organization strategies. Therefore, it has been postulated that story recall tests are more related to temporal lobe functions, and word-list learning tasks to frontal lobe functions. The aim of the present study was to evaluate the microstructural integrity of UF in non-demented patients with ALS measured by DTI and examine the association between UF microstructure and verbal memory function measured by neuropsychological assessment.
Method Participants Twenty eight consecutive patients with sporadic ALS were recruited after written informed consent in this prospective study, which was conducted in compliance with the regulations of the local ethics committee and in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Inclusion criteria were: (1) a diagnosis of definite, probable, and probable laboratory supported ALS, based on the revised El Escorial criteria (Brooks et al. 2000); (2) absence of other neurologic conditions affecting cognition (other than ALS); (3) no serious psychiatric illness (e.g., major depression, schizophrenia) or other systemic disease; (4) no family history of ALS, (5) absence of psychoactive drugs or other medication that could affect mental status; (6) absence of dementia (Mini Mental State Examination > 25; spared activities of daily living, social and personal conduct and insight based on patients’ and relatives’ reports; absence of signs of semantic dementia or progressive non-fluent aphasia based on quantitative and qualitative analysis of Wechsler Adult
Intelligence Scale (WAIS) Vocabulary performance and discourse speech; absence of behavioral dysfunction based on relatives’ reports); (7) absence of severe motor deficits (upper extremities, dysarthria) that could interfere with cognitive performance; (8) absence of significant respiratory failure (measured for ALS through forced vital capacity
ORIGINAL RESEARCH
Uncinate fasciculus microstructure and verbal episodic memory in amyotrophic lateral sclerosis: a diffusion tensor imaging and neuropsychological study Foteini Christidi & Ioannis Zalonis & Stavroula Kyriazi & Michalis Rentzos & Efstratios Karavasilis & Elisabeth A. Wilde & Ioannis Evdokimidis
# Springer Science+Business Media New York 2013
Abstract The present study evaluates the integrity of uncinate fasciculus (UF) and the association between UF microstructure and verbal episodic memory (as one of the cognitive functions linked to UF) in non-demented patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). We studied 21 patients with ALS and 11 healthy, demographicallycomparable volunteers. Fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity were the DTI metrics examined. Episodic memory was evaluated with Babcock Story Recall Test and Rey Auditory Verbal Learning Test (RAVLT) for patients; measures of immediate and delayed recall and retention for both tests and sum of words recalled through five learning trials for RAVLT were considered. Patients with ALS showed significant bilateral reduction of axial diffusivity in the UF as compared to controls. Furthermore, there were several significant relations between various DTI metrics (mostly in left hemisphere) and memory measures (specifically for the RAVLT). UF microstructural changes may contribute to ALSrelated memory impairment, with word-list learning performance F. Christidi : M. Rentzos : I. Evdokimidis First Department of Neurology, Aeginition Hospital, Medical School, National and Kapodistrian University, Athens, Greece F. Christidi (*) : I. Zalonis Neuropsychological Laboratory, First Department of Neurology, Aeginition Hospital, Medical School, National and Kapodistrian University, 72-74 Vas. Sophias Avenue, Athens 115 28, Greece e-mail: [email protected] S. Kyriazi : E. Karavasilis Radiology Research Unit, Medical Imaging Department, Evgenidion Hospital, National and Kapodistrian University, Athens, Greece E. A. Wilde Departments of Physical Medicine and Rehabilitation, Neurology and Radiology, Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
relying more upon the integrity of frontal and temporal connections than memory components associated with story recall. Keywords Uncinate fasciculus . Memory function . Diffusion tensor imaging . Amyotrophic lateral sclerosis
Introduction In the past decade, advanced magnetic resonance imaging (MRI) techniques, such as diffusion tensor imaging (DTI), have allowed detection and quantification of sub-clinical motor neuron damage and provided further support for extra-motor involvement in patients with amyotrophic lateral sclerosis (ALS). DTI measures the magnitude and orientation of anisotropic water diffusion in biological tissues and permits the exploration of white matter (WM) pathways in vivo. DTI-derived parameters, such as fractional anisotropy (FA), apparent diffusion coefficient (ADC), and axial and radial diffusivity (DA and DR, respectively) have been deemed proxies for WM integrity (Alexander et al. 2007), and they can be used to evaluate the integrity or disruption of fiber tracts (Mori and Zhang 2006). Regarding extra-motor involvement in ALS, decreased FA values have been reported in the corpus callosum and in WM regions in the frontal and temporal lobes, and increased ADC values have been found in frontal and temporal WM regions (Agosta et al. 2010a; Li et al. 2012; Tsermentseli et al. 2012). The uncinate fasciculus (UF) connects the inferior frontal gyrus and the inferior surfaces of the frontal lobe with the anterior portions of the temporal lobe (Schmahmann et al. 2007). Despite the fact that its role in cognition remains still unclear, there is increasing evidence of its involvement in episodic memory formation and retrieval (Diehl et al. 2008; Fink et al. 2010; Fujie et al. 2008; Nestor et al. 2004; Squire
Brain Imaging and Behavior
and Zola-Morgan 1991). Contrary to the relatively consistent finding of executive dysfunction in patients with ALS (Irwin et al. 2007; Raaphorst et al. 2010), there is variable evidence for deficits in memory functions (Abe et al. 1997; Abrahams et al. 1997; Chari et al. 1996; Dary-Auriol et al. 1997; Frank et al. 1997; Hanagasi et al. 2002; Iwasaki et al. 1990; Kew et al. 1993; Ludolph et al. 1992; Mantovan et al. 2003; Massman et al. 1996; Paulus et al. 2002; Rakowicz and Hodges 1998). Few studies have investigated the nature of memory impairment in these patients; most of them support an encoding or retrieval deficit, mostly related to frontal dysfunction (Mantovan et al. 2003), yet consolidation memory difficulties cannot be excluded (Christidi et al. 2012). In clinical neuropsychological practice, verbal memory is routinely examined through story recall and word-list learning tests, which although initially thought to address interchangeable functions (Delis et al. 1988), are now considered different (Helmstaedter et al. 2009; Randolph et al. 1994; Wicklund et al. 2006). Contrary to the inherent organization of the story recall material, word-list learning tests include either related or unrelated words requiring self-generation organization strategies. Therefore, it has been postulated that story recall tests are more related to temporal lobe functions, and word-list learning tasks to frontal lobe functions. The aim of the present study was to evaluate the microstructural integrity of UF in non-demented patients with ALS measured by DTI and examine the association between UF microstructure and verbal memory function measured by neuropsychological assessment.
Method Participants Twenty eight consecutive patients with sporadic ALS were recruited after written informed consent in this prospective study, which was conducted in compliance with the regulations of the local ethics committee and in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Inclusion criteria were: (1) a diagnosis of definite, probable, and probable laboratory supported ALS, based on the revised El Escorial criteria (Brooks et al. 2000); (2) absence of other neurologic conditions affecting cognition (other than ALS); (3) no serious psychiatric illness (e.g., major depression, schizophrenia) or other systemic disease; (4) no family history of ALS, (5) absence of psychoactive drugs or other medication that could affect mental status; (6) absence of dementia (Mini Mental State Examination > 25; spared activities of daily living, social and personal conduct and insight based on patients’ and relatives’ reports; absence of signs of semantic dementia or progressive non-fluent aphasia based on quantitative and qualitative analysis of Wechsler Adult
Intelligence Scale (WAIS) Vocabulary performance and discourse speech; absence of behavioral dysfunction based on relatives’ reports); (7) absence of severe motor deficits (upper extremities, dysarthria) that could interfere with cognitive performance; (8) absence of significant respiratory failure (measured for ALS through forced vital capacity
