Kie Honjo

Trail Making Test Elucidates Neural Substrates of Specific Poststroke Executive Dysfunctions

Background and Purpose— Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. Methods— One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute–subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. Results— Multiple linear regression analyses were completed. Although larger infarcts (&bgr;=0.37, P<0.0001) were associated with slower processing speed, cholinergic hyperintensities projections scale severity (&bgr;=0.39, P<0.0001) was associated with all metrics of set shifting. Left superior longitudinal fasciculus damage, however, was only associated with the difference score (&bgr;=0.17, P=0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. Conclusions— In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.

Congenital absence of the mammillary bodies: a novel finding in a well-studied case of developmental amnesia.

Individuals with developmental amnesia experience compromised development of episodic memory for details of personal life events, believed to relate to changes to the hippocampus after birth. Here we report the very rare discovery of aplasia of the mammillary bodies, hypogenesis of the fornix, and abnormal hippocampal shape and orientation in H.C., a well-documented case of selectively compromised episodic memory development who is the subject of numerous published empirical articles. These anatomical abnormalities are highly suggestive of disrupted extended hippocampal system development very early in gestation, despite an original diagnosis of developmental amnesia and assumed perinatal hypoxia. These findings provide a unique window into the normal function of the mammillary bodies, fornices, and related anterior nuclei of the thalamus bilaterally. The results also encourage re-examination of the pathological basis of developmental amnesia in other cases reported in the literature.

Progression of limb apraxia in corticobasal syndrome: neuropychological and functional neuroimaging report of a case series

The current study described the progression of limb apraxia in seven corticobasal syndrome patients through a comprehensive battery, including both gesture production tasks and conceptual tool/action knowledge tasks. The examination of the behavioral and neuroimaging (SPECT) data revealed two patient subgroups. One group consisted of patients with preserved conceptual tool/action knowledge, relatively mild gesture production and neuropsychological deficits with few significantly hypoperfused regions of interest. The other group consisted of those whose conceptual tool/action knowledge and general cognition eventually deteriorated and who were quite severely affected in their gesture production performance. These patients were characterized by bilateral hypoperfusion in parietal regions and in one case bilateral anterior cingulate regions.

Variability in stroke motor outcome is explained by structural and functional integrity of the motor system

Biomarkers that represent the structural and functional integrity of the motor system enable us to better assess motor outcome post-stroke. The degree of overlap between the stroke lesion and corticospinal tract (CST Injury) is a measure of the structural integrity of the motor system, whereas the left-to-right motor cortex resting state connectivity (LM1-RM1 rs-connectivity) is a measure of its functional integrity. CST Injury and LM1-RM1 rs-connectivity each individually correlate with motor outcome post-stroke, but less is understood about the relationship between these biomarkers. Thus, this study investigates the relationship between CST Injury and LM1-RM1 rs-connectivity, individually and together, with motor outcome. Twenty-seven participants with upper limb motor deficits post-stroke completed motor assessments and underwent MRI at one time point. CST Injury and LM1-RM1 rs-connectivity were derived from T1-weighted and resting state functional MRI scans, respectively. We performed hierarchical multiple regression analyses to determine the contribution of each biomarker in explaining motor outcome. The interaction between CST Injury and LM1-RM1 rs-connectivity does not significantly contribute to the variability in motor outcome. However, inclusion of both CST Injury and LM1-RM1 rs-connectivity explains more variability in motor outcome, than either alone. We suggest both biomarkers provide distinct information about an individual’s motor outcome.

Neural coupling between contralesional motor and frontoparietal networks correlates with motor ability in individuals with chronic stroke

Movement is traditionally viewed as a process that involves motor brain regions. However, movement also implicates non-motor regions such as prefrontal and parietal cortex, regions whose integrity may thus be important for motor recovery after stroke. Importantly, focal brain damage can affect neural functioning within and between distinct brain networks implicated in the damage. The aim of this study is to investigate how resting state connectivity (rs-connectivity) within and between motor and frontoparietal networks are affected post-stroke in correlation with motor outcome. Twenty-seven participants with chronic stroke with unilateral upper limb deficits underwent motor assessments and magnetic resonance imaging. Participants completed the Chedoke-McMaster Stroke Assessment as a measure of arm (CMSA-Arm) and hand (CMSA-Hand) impairment and the Action Research Arm Test (ARAT) as a measure of motor function. We used a seed-based rs-connectivity approach defining the motor (seed=contralesional primary motor cortex (M1)) and frontoparietal (seed=contralesional dorsolateral prefrontal cortex (DLPFC)) networks. We analyzed the rs-connectivity within each network (intra-network connectivity) and between both networks (inter-network connectivity), and performed correlations between: a) intra-network connectivity and motor assessment scores; b) inter-network connectivity and motor assessment scores. We found: a) Participants with high rs-connectivity within the motor network (between M1 and supplementary motor area) have higher CMSA-Hand stage (z=3.62, p=0.003) and higher ARAT score (z=3.41, p=0.02). Rs-connectivity within the motor network was not significantly correlated with CMSA-Arm stage (z=1.83, p>0.05); b) Participants with high rs-connectivity within the frontoparietal network (between DLPFC and mid-ventrolateral prefrontal cortex) have higher CMSA-Hand stage (z=3.64, p=0.01). Rs-connectivity within the frontoparietal network was not significantly correlated with CMSA-Arm stage (z=0.93, p=0.03) or ARAT score (z=2.53, p=0.05); and c) Participants with high rs-connectivity between motor and frontoparietal networks have higher CMSA-Hand stage (rs=0.54, p=0.01) and higher ARAT score (rs=0.54, p=0.009). Rs-connectivity between the motor and frontoparietal networks was not significantly correlated with CMSA-Arm stage (rs=0.34, p=0.13). Taken together, the connectivity within and between the motor and frontoparietal networks correlate with motor outcome post-stroke. The integrity of these regions may be important for an individuals motor outcome. Motor-frontoparietal connectivity may be a potential biomarker of motor recovery post-stroke.

The effects of music‐supported therapy on motor, cognitive, and psychosocial functions in chronic stroke

Neuroplasticity accompanying learning is a key mediator of stroke rehabilitation. Training in playing music in healthy populations and patients with movement disorders requires resources within motor, sensory, cognitive, and affective systems, and coordination among these systems. We investigated effects of music‐supported therapy (MST) in chronic stroke on motor, cognitive, and psychosocial functions compared to conventional physical training (GRASP). Twenty‐eight adults with unilateral arm and hand impairment were randomly assigned to MST (n = 14) and GRASP (n = 14) and received 30 h of training over a 10‐week period. The assessment was conducted at four time points: before intervention, after 5 weeks, after 10 weeks, and 3 months after training completion. As for two of our three primary outcome measures concerning motor function, all patients slightly improved in Chedoke–McMaster Stroke Assessment hand score, while the time to complete Action Research Arm Test became shorter in the MST group. The third primary outcome measure for well‐being, Stroke Impact Scale, was improved for emotion and social communication earlier in MST and coincided with the improved executive function for task switching and music rhythm perception. The results confirmed previous findings and expanded the potential usage of MST for enhancing quality of life in community‐dwelling chronic‐stage survivors.

Commentary on the letter for Alzheimer's disease and infection: Do infectious agents contribute to progression of Alzheimer's disease?

We thank Professor Itzhaki and Dr Wozniak for their interest in our article and for updating our review with recent publications with regards to the association between herpes simplex virus type 1 (HSV-1) and Alzheimer’s disease (AD). We agree that these latest results of HSV-1 are very important to confirm our hypothesis because previous studies have not consistently shown positive results. Knowing that APOE34 affects the brain vulnerability to many other brain injuries and that APOE34 is a well-established genetic risk factor for sporadic AD, this interaction is strong evidence. As Professor Itzhaki and her colleagues showed, the HSV-1 DNA is not exclusively located in the plaques in AD brains (72%) but also in plaques in normal brains (24%). Other results showed that 90% of plaques in AD brains and 80% in aged normal subjects contain viral DNA, meaning that 10% of plaques in AD brains and 20% in aged normal subjects do not contain viral DNA. These viral DNA-free plaques could be caused by other factors such as other infectious agents or acquired (ischemic-metabolic or mechanical-traumatic) brain injuries.