Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson's disease.

BACKGROUND: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson's disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. OBJECTIVES: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. METHODS: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. 11C-PE2I binding potential (BPND) was calculated for each participant. PD patients were assessed for disease severity. RESULTS: At baseline, PD patients with greater dopaminergic deficits, as measured with 11C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. CONCLUSIONS: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression

Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson’s disease

Background: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson’s disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. Objectives: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. Methods: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. 11CPE2I binding potential (BPND) was calculated for each participant. PD patients were assessed for disease severity. Results: At baseline, PD patients with greater dopaminergic deficits, as measured with 11C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. Conclusions: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression

Aberrant Function of Learning and Cognitive Control Networks Underlie Inefficient Cognitive Flexibility in Anorexia Nervosa: A Cross-Sectional fMRI Study

Objectives People with Anorexia Nervosa exhibit difficulties flexibly adjusting behaviour in response to environmental changes. This has previously been attributed to problematic behavioural shifting, characterised by a decrease in fronto-striatal activity. Additionally, alterations of instrumental learning, which relies on fronto-striatal networks, may contribute to the observation of inflexible behaviour. The authors sought to investigate the neural correlates of cognitive flexibility and learning in Anorexia Nervosa. Method Thirty-two adult females with Anorexia Nervosa and thirty-two age-matched female control participants completed the Wisconsin Card Sorting Task whilst undergoing functional magnetic resonance imaging. Event-related analysis permitted the comparison of cognitive shift trials against those requiring maintenance of rule-sets and allowed assessment of trials representing learning. Results Although both groups performed similarly, we found significant interactions in the left middle frontal gyrus, precuneus and superior parietal lobule whereby blood-oxygenated-level dependent response was higher in Anorexia Nervosa patients during shifting but lower when maintaining rule-sets, as compared to healthy controls. During learning, posterior cingulate cortex activity in healthy controls decreased whilst increasing in the Anorexia Nervosa group, whereas the right precuneus exhibited the opposite pattern. Furthermore, learning was associated with lower blood-oxygenated-level dependent response in the caudate body, as compared to healthy controls. Conclusions People with Anorexia Nervosa display widespread changes in executive function. Whilst cognitive flexibility appears to be associated with aberrant functioning of the fronto-parietal control network that mediates between internally and externally directed cognition, fronto-striatal alterations, particularly within the caudate body, were associated with instrumental learning. Together, this shows how perseverative tendencies could be a substrate of multiple high-order processes that may contribute to the maintenance of Anorexia Nervosa

Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson's disease.

BACKGROUND: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson's disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. OBJECTIVES: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. METHODS: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. 11C-PE2I binding potential (BPND) was calculated for each participant. PD patients were assessed for disease severity. RESULTS: At baseline, PD patients with greater dopaminergic deficits, as measured with 11C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. CONCLUSIONS: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression

Demographic and questionnaire measures for Anorexia Nervosa (AN) and Healthy Control (HC) groups.

<p>Score ranges: Hospital Anxiety and Depression Scale (HADS; 0–21), Eating Disorder Examination Questionnaire (EDE-Q; 0–6), Cognitive Flexibility Scale (CFS; 0–72)</p><p>(-) indicates where all participants scored 0</p><p>IQR = inter-quartile range; S.D. = standard deviation; BMI = body mass index; NART = national adult reading test</p><p>(*) indicates results that remain significant after Bonferroni multiple comparison correction</p><p>^a Data based on 31AN and 32HC</p><p>^b Data based on 28AN</p><p>Demographic and questionnaire measures for Anorexia Nervosa (AN) and Healthy Control (HC) groups.</p

fMRI results of cognitive flexibility comparisons.

<p>(A): Axial slices and line graphs showing significant group (Anorexia Nervosa, Healthy Control) x event (Efficient Shift [<i>Eff-Sh</i>], First Correct [<i>F-Corr</i>]) interactions of BOLD response (SSQ value) in the left middle frontal gyrus (BA9, Peak activation Talairach coordinates = -40, 22, 26, cluster size = 14, p = 0.0069), left inferior precuneus (BA7, Peak activation Talairach coordinates = -25, -56, 26, cluster size = 34, p = 0.0029) and left superior parietal lobule extending into the precuneus (BA7, Peak activation Talairach coordinates = -18, -67, 48, cluster size = 17, p = 0.0078). (B): Sagittal slices and bar charts illustrating the BOLD response during <i>SiS-P</i> and <i>Rec-P</i> and corresponding activity during <i>Eff-Sh</i> in the left middle frontal gyrus, left inferior precuneus and left superior parietal lobule. Functional data were thresholded to yield less than 1 false positive cluster per map and overlaid onto a high resolution single subject T1 structural image in Talairach space.</p

Regions showing a significant difference between Efficient Shift (<i>Eff-Sh)</i> and First Correct (<i>F-Corr</i>) trials.

<p>Efficient Shift <i>(Eff-Sh)</i>; First Correct <i>(F-Corr)</i>; Anorexia Nervosa (AN); Healthy Controls (HC)</p><p>All listed regions survived correction for multiple comparisons.</p><p>Regions showing a significant difference between Efficient Shift (<i>Eff-Sh)</i> and First Correct (<i>F-Corr</i>) trials.</p

Time course of a WCST trial and events of interest for behavioural and fMRI analysis.

<p>Each example presents the current rule chosen by the program (‘correct rule’) with concurrent trial-by-trial participant responses (‘chosen rule’), illustrating different WCST ‘event types’. Note that for event-related fMRI analysis, each event is modelled as the period between two consecutive responses and the ‘event type’ is defined by the combination of the two responses. EXAMPLE A: I) Efficient Shifts (<i>Eff-Sh</i>) were when participants changed sorting rules following negative feedback to one that had not been previously tested. II) Stuck-in-set perseverations (<i>SiS-P</i>) occurred if the same sorting rule that was incorrect in the previous trial was applied in the subsequent trial. III) First correct sort (<i>F-Corr</i>) of a new set. IV) Second correct sort (<i>S-Corr</i>) follows first correct sort. V) fMRI baseline (<i>Baseline</i>) was designated as trials 3–8 of a string of 8 consecutive correct sorts. EXAMPLE B: VI) Recurrent perseverations (<i>Rec-P</i>) constituted shifts to another sorting rule following incorrect feedback, but to one that had been tested two trials previously and already fed back as incorrect. EXAMPLE C: VII) Error Set trials (<i>Error Set</i>) were correct sorts not included as baseline trials due to occurrence of ‘loss of set’ errors within that particular set. VIII) Loss of set (<i>Loss of set</i>) trials are shifts to a different rule following positive feedback.</p

WCST performance and reaction time measures for Anorexia Nervosa (AN) and Healthy Control (HC) groups.

<p>IQR = inter-quartile range; S.D. = standard deviation</p><p>(*) indicates results that remain significant after Bonferroni multiple comparison correction</p><p>^a Data based on 16AN and 16HC; the remaining participants committed 0 errors</p><p>^b Data based on 11AN and 13HC; the remaining participants committed 0 errors</p><p>^c Data based on 26AN and 25HC; the remaining participants committed 0 errors</p><p>WCST performance and reaction time measures for Anorexia Nervosa (AN) and Healthy Control (HC) groups.</p

Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson’s disease

Background: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson’s disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. Objectives: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. Methods: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. 11CPE2I binding potential (BPND) was calculated for each participant. PD patients were assessed for disease severity. Results: At baseline, PD patients with greater dopaminergic deficits, as measured with 11C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. Conclusions: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression