Elsevier

NeuroImage

Volume 55, Issue 2, 15 March 2011, Pages 462-467
NeuroImage

Patterns of cortical thickness and surface area in early Parkinson's disease

https://doi.org/10.1016/j.neuroimage.2010.12.043Get rights and content

Abstract

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder diagnosed on the basis of motor symptoms, but that also includes cognitive and visuo-spatial deficits. Though PD is known to initially affect subcortical regions, the cortex also exhibits neuronal loss in the course of the disease as post mortem studies have shown. So far, PD-related pattern of cortical damage remains unclear, because of disease-caused heterogeneity, and also in part because of methodological issues such as the limitations of Voxel Based Morphometry. Here corticometry was used, a technique that decouples local surface from thickness, to obtain a better picture of PD corticomorphometric patterns.

We acquired MRI volumes for 33 healthy controls (HC) and 49 PD patients, extracted local cortical thickness and surface area and modeled both of them as a function of group and age for each participant. Cortical thickness averaged on the whole cortex did not differ between the two groups while mean surface area was significantly larger in the PD group. The bilateral parietal lobule, the right superior frontal gyrus, the left cingulate cortex and the left insular cortex exhibited larger local surface area in the PD group. The right precuneus exhibited cortical thinning associated with age in the PD group and not in the HC group. Furthermore, cortical thinning was observed in the PD group compared with the control group in the left medial supplementary motor area (SMA) and in the right dorsal pre-SMA. Finally, we found the left temporal pole thickness to correlate with disease duration, as well as the bilateral occipital cortex and Broca's area.

These results suggest that PD etiology is associated with specific cortical alterations, which could account for cognitive deficits that arise as the disease evolves. Finally, our results observed in the occipital cortex as a function of disease duration may indicate the increase in PD-related visuo-spatial deficits, which can sometimes result in hallucinations later on in the disease. In the future, MRI-generated corticometry, combined with additional behavioral markers, may prove to be a useful diagnosis tool to characterize the evolution of motor and cognitive deficits in PD.

Research Highlights

►Mean cortical thickness is similar in patients with Parkinson's disease vs. controls. ►Mean cortical surface is larger in patients with Parkinson's disease vs. controls. ►A network of cortical regions exhibits PD-related surface expansion. ►A network of cortical regions exhibits thinning related to disease duration.

Introduction

Parkinson's disease (PD) is a neurodegenerative disease diagnosed on the basis of a specific array of motor symptoms (tremor, rigidity, bradykinesia and loss of postural reflexes). The destruction of Substantia Nigra pars compacta (SNpc) dopaminergic neurons is a hallmark of PD (Fearnley and Lees, 1991). Such destruction induces altered activity in a basal-ganglia thalamocortical closed circuit including the SNpc (Alexander et al., 1986, Lehericy et al., 2004b). Furthermore, non-motor symptoms appear in the course of the disease, such as cognitive impairments, that have been associated with impaired striatal and cortical function and metabolism in PD using functional neuroimaging (Monchi et al., 2004, Monchi et al., 2001, Huang et al., 2007). However, the existence of a PD-related pattern of cortical degeneration remains unclear.

While it is established that in early PD, no global brain atrophy is detectable (Dalaker et al., 2009), numerous neuroimaging studies using magnetic resonance imaging have investigated the extent of localized cortical atrophy in PD. Voxel based morphometry (VBM) is a technique based on the delineation of grey matter and normalization, to assess grey matter density and atrophy (Ashburner et al., 2000). It has been applied by different researchers to reveal various regions of cortical atrophy in a non-demented PD population compared to healthy controls: left anterior cingulate (Summerfield et al., 2005), left rectus and parahippocampal gyrus and right inferior frontal gyrus (Nagano-Saito et al., 2005), the right frontal lobe (BA 45, 47, 10) (Burton et al., 2004) but sometimes no cortical atrophy was observed (Camicioli et al., 2009). Known caveats of VBM such as non-specific spatial smoothing (Davatzikos, 2004) that mixes voxels far apart on the plane (on different hemispheres, or on different sides of a sulcus) could explain these variabilities and the lack of a consistent portrait of damage on the cerebral cortex.

Corticometry, a new structural analysis technique using MRI anatomical scans, has recently attracted interest from the community investigating neuronal degeneration. Local cortical thickness reflects the VBM notion of local grey matter (GM) volume. Local surface area analysis assesses local folding and gives access to geometrical properties of the plane. The separate analysis of these orthogonal characteristics allows for a study of the cortex that respects topology and therefore enhances reliability and sensitivity. To date, cortical thickness analysis has successfully addressed questions related to neurodegenerative pathologies known to affect the cortical plane (Bernhardt et al., 2009, Lerch et al., 2008) but to the best of our knowledge, it has not been used to study the group-wise effect of PD on the cortex.

We hypothesized that a network of cortical regions would exhibit alterations due to PD. The supplementary motor area (SMA) is located in the medial premotor cortex, above the cingulate gyrus, and is involved in the generation of self-initiated, complex and sequential movements (Nachev et al., 2008, Tanji and Hoshi, 2001). It has direct projections to the motor cortex, arcuate premotor area and to the spinal cord, and is considered part of the motor cortico-striatal loop (Lehericy et al., 2004a). Electroencephalography measures have shown anomalies (Dick et al., 1989) and metabolic decrease has been shown in this region in the Parkinson's brain associated with cognitive deficits (Lozza et al., 2004). Furthermore, functional MRI studies have revealed activation decreases in the SMA in PD patients exhibiting depression (Cardoso et al., 2009, Eckert et al., 2007). Based on these evidences, we expected to detect consistent damage in this region or its vicinity using neuroanatomical imaging in early PD patients. Its medial localization would make damage detection unreliable using VBM, since this technique mixes gray matter volume information from both hemispheres. Additionally, studies based on regional cerebral blood flow (rCBF) analysis have shown that the greatest decrease in metabolic activity observed in PD occurs in the occipital cortex (Bohnen et al., 1999, Nagamachi et al., 2008). This region did not exhibit any atrophy in VBM studies of PD, and is also localized partially on the medial wall. Finally, based on post-mortem neuropathological evaluation, Braak and colleagues (Braak et al., 2003) have proposed a 6-stages model of Parkinson's disease neuropathology progression. This model relies on the analysis of the spatial distribution of induction sites of Lewy bodies and neurites deposits in the brain. Although it is still unclear whether these structures are the direct cause of neuronal degeneration or a by-product, in the process, cortical pathology would begin in the temporal mesocortex regions (stage 4), continue in the prefrontal cortex (stage 5), and finally in primary sensory and premotor areas in (stage 6). Therefore, we expected corticometry to reveal changes related to the disease progression in this network of regions.

This study aimed to address two issues: whether corticometry can identify a stable pattern of cortical changes in PD consistent with previous studies, notably on the medial wall and whether this pattern could be associated to age and other metrics linked to the disease (duration, motor symptoms, and depressive symptoms).

Section snippets

Study population

We recruited 49 non-demented PD patients at the early stages of the disease (16 females) and 33 healthy subjects (16 females). Table 1 gives clinical and demographic details of the PD and control groups. All PD participants met the core assessment program for surgical interventional therapy criteria for the diagnosis of idiopathic PD (Defer et al., 1999, Langston et al., 1992) and the UK brain bank criteria for the diagnosis of PD (Hughes et al., 1992). Out of the 49 patients 45 were taking

Results

There was no difference of global cortical thickness between the two groups (mean cortical thickness in the PD group = 2.88 ± 0.15 mm, in the HC group = 2.88 ± 0.11 mm, p > 0.82, Fig. 1). In both groups, global cortical thickness was correlated with age (in both cases p < 0.001) without any interaction between age and condition (p > 0.35).

Mean cortical surface area was significantly larger in the PD than in the HC group (2.30 ± 0.18 mm2 vs. 2.19 ± 0.16 mm2; p < 0.005) but it did not correlate with age in either group

Discussion and conclusion

The results of this study showed that while global cortical thickness is preserved in an early, non-demented PD population compared with a healthy population, global surface area increased. Furthermore, we found local areas exhibiting surface expansion associated with the disease, in the left cingulate cortex, the bilateral superior parietal cortex, the left insula and the right superior frontal gyrus. We also found a thinning trend of the cortex associated to the disease in the left SMA and in

Acknowledgments

This work was supported by operating grants from the Canadian Institutes for Health Research to OM (MOP-81114) and to JFG (MOP-84482). The authors would like to thank Drs. Sylvain Chouinard, Ron Postuma and Kalvin Melmed for help with patient recruitment, the staff at the Functional Neuroimaging Unit at the CRIUGM, Felix Carbonnel, Boris Bernhardt, Christophe Bedetti and Clotilde Degroot for technical assistance, as well as all the participants of the study for their time and dedication.

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