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Review
, 35 (1), 70-85

The Neural Circuitry of Executive Functions in Healthy Subjects and Parkinson's Disease

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Review

The Neural Circuitry of Executive Functions in Healthy Subjects and Parkinson's Disease

Sandra E Leh et al. Neuropsychopharmacology.

Abstract

In our constantly changing environment, we are frequently faced with altered circumstances requiring generation and monitoring of appropriate strategies, when novel plans of action must be formulated and conducted. The abilities that we call upon to respond accurately to novel situations are referred to as 'executive functions', and are frequently engaged to deal with conditions in which routine activation of behavior would not be sufficient for optimal performance. Here, we summarize important findings that may help us understand executive functions and their underlying neuronal correlates. We focus particularly on observations from imaging technology, such as functional magnetic resonance imaging, position emission tomography, diffusion tensor imaging, and transcranial magnetic stimulation, which in the past few years have provided the bulk of information on the neurobiological underpinnings of the executive functions. Further, emphasis will be placed on recent insights from Parkinson's disease (PD), in which the underlying dopaminergic abnormalities have provided new exciting information into basic molecular mechanisms of executive dysfunction, and which may help to disentangle the cortical/subcortical networks involved in executive processes.

Figures

Figure 1
Figure 1
Cytoarchitectonic map of the lateral surface of the prefrontal cortex of (a) the human brain and (b) the macaque monkey brain by Petrides and Pandya (1994). Ai, inferior arcuate sulcus; CS, central sulcus; SF, Sylvian fissure. (Adapted and reproduced with permission from Petrides and Pandya, 1994).
Figure 2
Figure 2
Summary diagrams showing the connectional relationships between the dorsal and the ventral architectonic trends of the prefrontal cortex and the caudate nucleus in the sagittal plane (adapted and reproduced with permission from Yeterian and Pandya, 1991).
Figure 3
Figure 3
Connectivity-based seed qualification of the caudate (a) and putamen (b) in six subjects (S1–S6). (a) Connections between DLPFC and dorsal-posterior caudate, and VLPFC and ventral-anterior caudate. (b) Connections between SMA and dorsal-posterior putamen, premotor area and medial putamen, and primary motor area and lateral putamen. (Adapted and reproduced with permission from Leh et al, 2007).
Figure 4
Figure 4
The top left panel displays the sites of the main prefrontal areas identified in the fMRI experiment during Wisconsin Card Sorting Task on a cortical surface rendering an MRI in standard stereotaxic space. The vertical blue lines indicate the anteroposterior level of the coronal sections in (a) and (b). The horizontal blue lines indicate the dorsoventral level of the sections displayed in (c) and (d). The focus in the mid-DLPFC is indicated by the red circle, in mid-VLPFC by the green circle, and in posterior PFC by the yellow circle. (a) Coronal section through the mid-DLPFC peak at Y=+30 mm. (b) Coronal section through the mid-VPFC peak at Y=+22 mm. (c) Horizontal section through the posterior PFC peak at z=+30 mm. (d) Horizontal section through the mid-VLPFC peak at z=+4 mm. Note also caudate and thalamus activation. All activation peaks shown here occurred during receiving negative feedback minus control feedback. IFS, inferior frontal sulcus; IPrS, inferior precentral sulcus. (Adapted and reproduced with permission from Monchi et al, 2001).
Figure 5
Figure 5
Axial (Z=16) and coronal (Y=10) sections of the statistical parametric map of the change in [11C]raclopride BP overlaid on the average MRI of all subjects in stereotaxic space. The figure displays the significant areas of striatal dopamine release (that is, reduction in [11C]raclopride BP) during the retrieval with shift condition compared with retrieval without shift condition (control) of Montreal Card Sorting Task: (a) left caudate: t=4.1; cluster size: 83 voxels, 670 mm3, (b) right caudate: t=4.1; cluster size: 42 voxels, 336 mm3, (c) right putamen: t=4.3; cluster size: 94 voxels, 752 mm3. (Adapted and reproduced with permission from Monchi et al, 2006a). On the bottom right, individual [11C]raclopride binding potentials for each subject during retrieval with shift condition and retrieval without shift condition (control), from the left caudate (p=0.03) and right putamen (p=0.01), extracted from a spherical region of interest (radius 5 mm) centered at the x, y, and z coordinates of the statistical peak revealed by the parametric map. On the top right, the Montreal Card Sorting Task. (a) An example of the cue card that appears for 3.5 s at the beginning of a block of retrieval trials. In this example, the cue card contains two red circles. The cue card changes for each block. (b, c) An example of two consecutive trials in the retrieval without shift condition. In (b), as the color red is the only attribute shared by the test card and the cue, matching must be based on color. In the following trial (c) the test card is red and the matching is performed according to the same rule. (d, e) An example of two consecutive retrieval trials with shift condition. (d) The test card contains four red stars and hence shares the color attribute with the cue card (containing two red circles, shown in (a). (e) On the subsequent trial, the test card shares a different attribute with the cue card (in this example ‘number').
Figure 6
Figure 6
Sagittal (X=6) and coronal (Y=24) section of the statistical parametric map of the change in [11C]FLB 457 BP overlaid on the average MRI of all subjects in standardized stereotaxic space. The figure displays the significant area of dopamine changes (that is, reduction in [11C]FLB 457 BP) during active task performance of the Montreal Card Sorting Task compared with the control task at the level of dorsal ACC. (Adapted and reproduced with permission from Ko et al (2009)). On the bottom, individual ACC-[11C]FLB 457 BP and mean±SE of ACC-[11C]FLB 457 BP during control and active task extracted from a spherical region of interest (r=3 mm) centered at the x, y, and z coordinates of the statistical peak (X=6, Y=26, Z=40) revealed by the parametric map (paired t-test, t(7)=3.85, *p=0.006).
Figure 7
Figure 7
Comparison between left DLPFC and vertex stimulation: (a) Comparison between left DLPFC and vertex stimulation (control condition). Sagittal (x=−12 and x=−22) and axial (z=14) sections of the statistical parametric map of the change in [11C]raclopride BP overlaid on the average MRI of all subjects in stereotaxic space. The figure displays the significant areas of striatal dopamine changes during Montreal Card Sorting Task performance after left DLPFC stimulation compared with vertex stimulation (control). (b) Comparison between right DLPFC and vertex stimulation showing the lack of changes in [11C]raclopride BP. (Adapted and reproduced with permission from Ko et al, 2008a).
Figure 8
Figure 8
Location of peaks within the retrieval with shift vs the retrieval without shift condition of the Montreal Card Sorting Task in PD and healthy controls during fMRI. Coronal sections are shown. The anatomical MRI images shown are the average of T1 acquisitions transformed into stereotaxic space for each group in the intra-group analysis and for both groups in the inter-group analysis. (a) Intra-group analysis. The images display significant activation in the left VLPFC and caudate nucleus in the control group, whereas none is observed in the Parkinson's disease group. They also show larger activations in the control group than in the patient group in the posterior cingulate cortex and the posterior parietal cortex bilaterally. (b) Inter-group analysis. Images display significantly greater activity in the control group vs the patient group in the left dorsolateral PFC and orbitofrontal cortex, as well as the right VLPFC, whereas no significantly increased activity is observed in the patient vs control group subtraction. (Adapted and reproduced with permission from Monchi et al, 2007).
Figure 9
Figure 9
Inverted U-shaped relationship between working memory (WM) performance and dopamine level in the DLPFC. The COMT met/met genotype is expected to confer a higher baseline dopamine level than the val/val genotype. This has opposing behavioral consequences in schizophrenics (SZ)/controls and those with early PD, suggesting that their relative positions on the curve differ. (Adapted and reproduced with permission from Williams-Gray et al, 2007).

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