The cortical projections of the inferior pulvinar and adjacent lateral pulvinar in the rhesus monkey (Macaca mulatta): an autoradiographic study.

An autoradiographic technique was used to determine superior colliculus (SC) and pulvinar projections in the rhesus monkey. SC projects bilaterally to the inferior pulvinar (PI) while occipital cortex projects to PI and the lateral pulvinar (PL). PI has sustaining, topographical projections to layers IV, III and I of areas 18 and 19 (and VI and I of 17) which agrees with the central representation of the visual hemifield and suggests that there is more than one hemifield representation in prestriate cortex. PL adjacent to PI also projects to the same cortical areas and layers, while the portion of PL extending into the caudal pole of the pulvinar projects to layers IV, III and I of areas 20 and 21. Thus, occipital cortices are associated by cortico-thalamocortical connections and also receive direct lemniscal input via SC-PI and the dorsal lateral geniculate nucleus (DLG), while inferotemporal areas 20 and 21 receive only cortico-thalamocortical connections. It is concluded that Stoffels' principle of lamellation holds and, that one pulvinar subdivision projects to several cortical areas, that adjacent pulvinar subdivisions have overlapping projections to these cortical areas and their layers and that the pulvinar also projects to the same cortical area as DLG but to different layers. These connections are similar to those in lower mammals but not to those in the squirrel monkey and bushbaby.

A comparison of the organization of the projections of the dorsal lateral geniculate nucleus, the inferior pulvinar and adjacent lateral pulvinar to primary visual cortex (area 17) in the macaque monkey.

Both anterograde and retrograde transport tracing methods were used to study the organization of the projections of the dorsal lateral geniculate (DLG), the inferior pulvinar and subdivisions of the lateral pulvinar to primary visual cortex (striate cortex or area 17). The DLG projects only to striate cortex. These projections are retinotopically organized, and do not extend to any cortical layers above layer IVA. In contrast the inferior pulvinar (PI) and the immediately adjacent portion of the lateral pulvinar (PL alpha 48) project to both striate and prestriate cortex. The projections from these two thalamic areas to the striate cortex are also retinotopically organized and exist in parallel with those from the DLG. In contrast to the DLG, the projections from PI and PL alpha terminate above layer IVA in striate cortex, i.e. layers I, II and III. In prestriate cortex the layers of termination include layers IV, III and I. The pulvinar terminations in layers II and III of area 17 occur in segregated patches as do the geniculate terminations in layers IVC and IVA. On the other hand the pulvinar terminations in layer I which overlie those in layers II and III of area 17 appeared to be continuous. Control studies show that the remainder of the lateral pulvinar overlying PL alpha does not project to striate cortex. It is concluded that there are 3 visuotopically organized inputs from the lateral thalamus to primary visual cortex and that each of these inputs have different layers of termination. The inputs from PI and DLG can convey direct retinal inputs while those from PI and PL alpha can also be involved in intrinsic cortico-thalamocortical connection with prestriate cortex. It remains, then that it cannot be tacitly assumed that the ascending inputs which influence the response properties of the primary cortical neurons arise solely from the dorsal lateral geniculate nucleus. It is also argued that these inputs to the supragranular layers may be excitatory as those from the DLG to the IVth layer.

An autoradiographic study of the projections of the pretectum in the rhesus monkey (Macaca mulatta): evidence for sensorimotor links to the thalamus and oculomotor nuclei.

Autordiographic tracing methods were used to determine the differential projections of the pretectal nuclei, in the rhesus monkey, in relation to their inputs. The sublentiform (SL) and olivary (ON) nuclei receive projections from the visual cortex, superior colliculus (SC) and equal bilateral projection from the retina. The nucleus of the posterior commissure (NPC) and its subdivisions do not receive any of these inputs. The projections of the pretectum involve a number of structures within the thalamus and brain stem and there are differences in the projection targets of the pretectal region which receives direct visual input (i.e., SL and ON) and the region which does not (i.e., nucleus of the posterior commissure, NPC). For example, while all pretectal regions project within the pretectum and to the SC, accessory oculomotor nuclei, reticular formation, intralaminar nuclei and hypothalamus, it is only the retinorecipient zone which projects to rostral regions such as the visceral oculomotor nuclei, the lateral pulvinar, the border between the lateral pulvinar and medial pulvinar, the oral pulvinar as well as to the thalamic reticular nucleus, ventral lateral geniculate nucleus, zona incerta and other structures. It is concluded that the retina, SC and cortex which influence the visceral oculomotor nuclei can only do so by virtue of their projections to the pretectum, and that any consideration of accommodative and pupillary reflexes must view the pretectum as an obligatory link through which various structures can influence the intrinsic musculature of the eye. In contrast to the SC, the pretectum does not project to any of the visual relay nuclei of the thalamus, such as the inferior pulvinar, which project to the visual cortices. Instead, the pretectum projects directly to visuomotor, visceromotor and arousal systems.

Cognitive performance of GBA mutation carriers with early-onset PD: the CORE-PD study.

OBJECTIVE: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). METHODS: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. RESULTS: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004). CONCLUSION: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.

Olfaction in Parkin heterozygotes and compound heterozygotes: the CORE-PD study.

BACKGROUND: While Parkinson disease (PD) is consistently associated with impaired olfaction, one study reported better olfaction among Parkin mutation carriers than noncarriers. Whether olfaction differs between Parkin mutation heterozygotes and carriers of 2 Parkin mutations (compound heterozygotes) is unknown. OBJECTIVE: To assess the relationship between Parkin genotype and olfaction in PD probands and their unaffected relatives. METHODS: We administered the University of Pennsylvania Smell Identification Test (UPSIT) to 44 probands in the Consortium on Risk for Early-Onset Parkinson Disease study with PD onset ≤50 years (10 Parkin mutation heterozygotes, 9 compound heterozygotes, 25 noncarriers) and 80 of their family members (18 heterozygotes, 2 compound heterozygotes, 60 noncarriers). In the probands, linear regression was used to assess the association between UPSIT score (outcome) and Parkin genotype (predictor), adjusting for covariates. Among family members without PD, we compared UPSIT performance in heterozygotes vs noncarriers using generalized estimating equations, adjusting for family membership, age, gender, and smoking. RESULTS: Among probands with PD, compound heterozygotes had higher UPSIT scores (31.9) than heterozygotes (20.1) or noncarriers (19.9) (p < 0.001). These differences persisted after adjustment for age, gender, disease duration, and smoking. Among relatives without PD, UPSIT performance was similar in heterozygotes (32.5) vs noncarriers (32.4), and better than in heterozygotes with PD (p = 0.001). CONCLUSION: Olfaction is significantly reduced among Parkin mutation heterozygotes with PD but not among their heterozygous relatives without PD. Compound heterozygotes with PD have olfaction within the normal range. Further research is required to assess whether these findings reflect different neuropathology in Parkin mutation heterozygotes and compound heterozygotes.

The relation between depression and parkin genotype: the CORE-PD study.

BACKGROUND: Mutations in parkin are a known genetic risk factor for early onset Parkinson's disease (EOPD) but their role in non-motor manifestations is not well established. Genetic factors for depression are similarly not well characterized. We investigate the role of parkin mutations in depression among those with EOPD and their relatives. METHODS: We collected psychiatric information using the Patient Health Questionnaire and Beck Depression Inventory II on 328 genotyped individuals including 88 probands with early onset PD (41 with parkin mutations, 47 without) and 240 first and second-degree relatives without PD. RESULTS: Genotype was not associated with depression risk among probands. Among unaffected relatives of EOPD cases, only compound heterozygotes (n = 4), and not heterozygotes, had significantly increased risk of depressed mood (OR = 14.1; 95% CI 1.2-163.4), moderate to severe depression (OR = 17.8; 95% CI 1.0-332.0), depression (score ≥ 15) on the Beck Depression Inventory II (BDI-II) (OR = 51.9; 95% CI 4.1-657.4), and BDI-II total depression score (ß = 8.4; 95% CI 2.4-11.3) compared to those without parkin mutations. CONCLUSIONS: Relatives of EOPD cases with compound heterozygous mutations and without diagnosed PD may have a higher risk of depression compared to relatives without parkin mutations. These findings support evidence of a genetic contribution to depression and may extend the phenotypic spectrum of parkin mutations to include non-motor manifestations that precede the development of PD.