Claudia C. Schmidt

Apraxia represents a core feature of Alzheimer’s disease (AD), a neurodegenerative disorder characterised by the accumulation of β-amyloid plaques and tau deposition. However, systematic descriptions of apraxic deficits in AD patients remain scarce. Here, we comprehensively investigate apraxia profiles and their link with cognitive impairment in patients with biomarker-verified Alzheimer’s pathology. We characterised the frequency and patterns of apraxic deficits in patients with biomarker-verified Alzheimer’s pathology using a battery of standardised apraxia tests. Demographic variables and apraxia scores were related to patients’ general cognitive impairment using hierarchical regression analysis. Apraxic deficits were found in 67% of patients with biomarker-verified Alzheimer’s pathology ( n = 63). Patients with Alzheimer’s pathology were more impaired in imitating finger gestures (than hand gestures: 89.2% vs. 80.0%, p < 0.001) and imitating complex hand movements (than single hand movements: 97.4% vs. 78.5%, p < 0.001), even when controlling for general cognitive impairment. Apraxia assessments explained about 60% of the variance in dementia severity, with performance in the KAS subtest of pantomiming object use (beta coefficient: 0.47, p = 0.001) and the DATE subtest for limb apraxia (beta coefficient: 0.37, p = 0.005) constituting significant predictors of general cognitive impairment. These findings emphasise the relevance of apraxia in patients with biomarker-verified Alzheimer’s pathology, revealing that praxis deficits predict general cognitive impairment in AD. Further research is warranted into the role of apraxia as a potential early diagnostic criterion in AD.

Background and Objectives: Apraxia is commonly attributed to left hemisphere lesions of the cortical fronto-temporo-parietal praxis networks or white matter lesions causing disconnections between cortical nodes. In contrast, the contribution of lesions to the subcortical gray matter, i.e., basal ganglia or thalamus, to apraxic deficits remains controversial. Here, we investigate whether damage to these subcortical gray matter structures (i.e., caudate nucleus, putamen, globus pallidus, thalamus) or the adjacent white matter tracts was associated with apraxic deficits. Methods: We identified patients with distinct subcortical lesions with and without apraxia from a large retrospective sample of sub-acute left hemisphere ischemic stroke patients (n = 194). To test which subcortical structures (caudate nucleus, putamen, globus pallidus, thalamus, and adjacent white matter tracts), when lesioned, contributed to apraxic deficits, we statistically compared the proportion of lesioned voxels within subcortical gray and white matter structures between the apraxic and non-apraxic patients. Results: Of the 194 stroke patients screened, 39 (median age = 65 years, range 30−82 years; median time post-stroke at the apraxia assessment = 7 days, range 1−44 days) had lesions confined to subcortical regions (gray and white matter). Eleven patients showed apraxic deficits when imitating gestures or pantomiming object use. Region-wise statistical lesion comparison (controlled for lesion size) revealed a more significant proportion of damage (‘lesion load’) in the caudate nucleus in apraxic stroke patients (mean difference = 6.9%, 95% confidence interval [CI] 0.4–13.3, P = 0.038, η_p² = 0.11). In contrast, apraxic patients had lower lesion load in the globus pallidus (mean difference = 9.9%, 95% CI 0.1–19.8, P = 0.048, η_p² = 0.10), while the lesion load in other subcortical structures (putamen, thalamus, adjacent white matter tracts) did not differ significantly between the apraxic and non-apraxic patients. Discussion: These findings provide new insights into the subcortical anatomy of apraxia following left hemisphere stroke, suggesting a specific contribution of caudate nucleus lesions to apraxic deficits.

While the role of cortical regions in cognitive control processes is well accepted, the contribution of subcortical structures (e.g., the striatum), especially to the control of response interference, remains controversial. Therefore, the present study aimed to investigate the cortical and particularly subcortical neural mechanisms of response interference control (including selective inhibition). Thirteen healthy young participants underwent event-related functional magnetic resonance imaging while performing a unimanual version of the Simon task. In this task, successful performance required the resolution of stimulus–response conflicts in incongruent trials by selectively inhibiting interfering response tendencies. The behavioral results show an asymmetrical Simon effect that was more pronounced in the contralateral hemifield. Contrasting incongruent trials with congruent trials (i.e., the overall Simon effect) significantly activated clusters in the right anterior cingulate cortex, the right posterior insula, and the caudate nucleus bilaterally. Furthermore, a region of interest analysis based on previous patient studies revealed that activation in the bilateral caudate nucleus significantly co-varied with a parameter of selective inhibition derived from distributional analyses of response times. Our results corroborate the notion that the cognitive control of response interference is supported by a fronto-striatal circuitry, with a functional contribution of the caudate nucleus to the selective inhibition of interfering response tendencies.

Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and caudate nucleus) modulates the inhibition of interfering responses and thereby contributes to an important aspect of cognitive control, namely response interference control. To further investigate the putative role of the striatum in the control of response interference, 23 patients with stroke-induced lesions of the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated so that control over response interference can be inferred from the reaction time costs in incongruent trials. Results showed that stroke patients responded overall slower and more erroneous than controls. The difference in response times (RTs) between incongruent and congruent trials (known as the Simon effect) was smaller in the ipsilesional/-lateral hemifield, but did not differ significantly between groups. However, in contrast to controls, stroke patients exhibited an abnormally stable Simon effect across the reaction time distribution indicating a reduced efficiency of the inhibition process. Thus, in stroke patients unilateral lesions of the striatum did not significantly impair the general ability to control response interference, but led to less efficient selective inhibition of interfering responses.

Background and Objective: Apraxia is a deficit of motor cognition leading to difficulties in actual tool use, imitation of gestures, and pantomiming object use. To date, little data exist regarding the recovery from apraxic deficits after stroke, and no statistical lesion mapping study investigated the neural correlate of recovery from apraxia. Accordingly, we here examined recovery from apraxic deficits, differential associations of apraxia task (imitation vs. pantomime) and effector (bucco-facial vs. limb apraxia) with recovery, and the underlying neural correlates. Methods: We assessed apraxia in 39 patients with left hemisphere (LH) stroke both at admission and approximately 11 days later. Furthermore, we collected clinical imaging data to identify brain regions associated with recovery from apraxic deficits using voxel-based lesion-symptom mapping (VLSM). Results: Between the two assessments, a significant recovery from apraxic deficits was observed with a tendency of enhanced recovery of limb compared to bucco-facial apraxia. VLSM analyses revealed that within the lesion pattern initially associated with apraxia, lesions of the left insula were associated with remission of apraxic deficits, whereas lesions to the (inferior) parietal lobe (IPL; supramarginal and angular gyrus) and the superior longitudinal fasciculus (SLF) were associated with persistent apraxic deficits. Conclusions: Data suggest that lesions affecting the core regions (and white matter) of the fronto-parietal praxis network cause more persistent apraxic deficits than lesions affecting other regions (here: the left insula) that also contribute to motor cognition and apraxic deficits.

Background: Worrying has been suggested to prevent emotional and elaborative processing of fears. In cognitive-behavioral therapy (CBT), generalized anxiety disorder (GAD) patients are exposed to their fears during the method of directed threat imagery by inducing emotional reactivity. However, studies investigating neural correlates of directed threat imagery and emotional reactivity in GAD patients are lacking. The present functional magnetic resonance imaging (fMRI) study aimed at delineating neural correlates of directed threat imagery in GAD patients.Method: Nineteen GAD patients and 19 healthy controls (HC) were exposed to narrative scripts of either disorder-related or neutral content and were encouraged to imagine it as vividly as possible.Results: Rating results showed that GAD patients experienced disorder-related scripts as more anxiety inducing and arousing than HC. These results were also reflected in fMRI data: Disorder-relatedv.neutral scripts elicited elevated activity in the amygdala, dorsomedial prefrontal cortex, ventrolateral prefrontal cortex and the thalamus as well as reduced activity in the ventromedial prefrontal cortex/subgenual anterior cingulate cortex in GAD patients relative to HC.Conclusion: The present study presents the first behavioral and neural evidence for emotional reactivity during directed threat imagery in GAD. The brain activity pattern suggests an involvement of a fear processing network as a neural correlate of initial exposure during directed imagery in CBT in GAD.