Altered intrinsic functional coupling between core neurocognitive networks in Parkinson\u27s disease

Parkinson3s disease (PD) is largely attributed to disruptions in the nigrostriatal dopamine system. These neurodegenerative changes may also have a more global effect on intrinsic brain organization at the cortical level. Functional brain connectivity between neurocognitive systems related to cognitive processing is critical for effective neural communication, and is disrupted across neurological disorders. Three core neurocognitive networks have been established as playing a critical role in the pathophysiology of many neurological disorders: the default-mode network (DMN), the salience network (SN), and the central executive network (CEN). In healthy adults, DMN–CEN interactions are anti-correlated while SN–CEN interactions are strongly positively correlated even at rest, when individuals are not engaging in any task. These intrinsic between-network interactions at rest are necessary for efficient suppression of the DMN and activation of the CEN during a range of cognitive tasks. To identify whether these network interactions are disrupted in individuals with PD, we used resting state functional magnetic resonance imaging (rsfMRI) to compare between-network connectivity between 24 PD participants and 20 age-matched controls (MC). In comparison to the MC, individuals with PD showed significantly less SN–CEN coupling and greater DMN–CEN coupling during rest. Disease severity, an index of striatal dysfunction, was related to reduced functional coupling between the striatum and SN. These results demonstrate that individuals with PD have a dysfunctional pattern of interaction between core neurocognitive networks compared to what is found in healthy individuals, and that interaction between the SN and the striatum is even more profoundly disrupted in those with greater disease severity

Salience and default mode network coupling predicts cognition in aging and Parkinson’s disease

OBJECTIVES: Cognitive impairment is common in Parkinson’s disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. METHODS: We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. RESULTS: PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson’s disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. CONCLUSIONS: Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson’s disease.Published versio

Which Way Was I Going? Contextual Retrieval Supports the Disambiguation of Well Learned Overlapping Navigational Routes

Groundbreaking research in animals has demonstrated that the hippocampus contains neurons that distinguish betweenoverlapping navigational trajectories. These hippocampal neurons respond selectively to the context of specific episodes despite interference from overlapping memory representations. The present study used functional magnetic resonanceimaging in humans to examine the role of the hippocampus and related structures when participants need to retrievecontextual information to navigate well learned spatial sequences that share common elements. Participants were trained outside the scanner to navigate through 12 virtual mazes from a ground-level first-person perspective. Six of the 12 mazes shared overlapping components. Overlapping mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required the retrieval of contextual information relevant to thecurrent navigational episode. Results revealed greater activation during the successful navigation of the overlapping mazes compared with the non-overlapping mazes in regions typically associated with spatial and episodic memory, including thehippocampus, parahippocampal cortex, and orbitofrontal cortex. When combined with previous research, the current findings suggest that an anatomically integrated system including the hippocampus, parahippocampal cortex, and orbitofrontal cortexis critical for the contextually dependent retrieval of well learned overlapping navigational routes

Incidence and Risk Factors Associated with a Second Squamous Cell Carcinoma or Basal Cell Carcinoma in Psoralen + Ultraviolet A Light-treated Psoriasis Patients

Psoralen + ultraviolet A-treated psoriasis patients are at increased risk for squamous cell carcinomas and basal cell carcinomas; however, the incidence and risk factors associated with second squamous cell carcinomas and basal cell carcinomas in this population are not well qualified. Incidence and risk factors for second squamous cell carcinomas and basal cell carcinomas were studied in a cohort of 1380 psoralen + ultraviolet A-treated psoriasis patients prospectively followed for over 20 y; 264 had a squamous cell carcinoma and 258 a basal cell carcinoma after beginning psoralen + ultraviolet A therapy. After a first squamous cell carcinoma, the risk of a second squamous cell carcinoma was 26% at 1 y, 62% at 5 y, and 75% at 10 y. Risk increased with high psoralen + ultraviolet A exposure prior to the first squamous cell carcinoma (hazard ratio 3.32, 95% confidence interval 1.53, 7.18). Higher rates of post-first squamous cell carcinoma psoralen + ultraviolet A treatment also were associated with greater risk (hazard ratio 1.56 for every additional 10 treatments per year for patients with low pre-first squamous cell carcinoma psoralen + ultraviolet A exposure, 95% confidence interval 1.35, 1.81). Patients exposed to high levels of tar and/or ultraviolet B before a first squamous cell carcinoma were also at higher risk (hazard ratio 1.72, 95% confidence interval 1.14–2.60). Risk of a second basal cell carcinoma was 21% at 1 y, 49% at 5 y, and 61% at 10 y. There was some evidence that high exposure to psoralen + ultraviolet A before a first basal cell carcinoma was associated with increased risk of second basal cell carcinoma (hazard ratio 1.45, 95% confidence interval 0.97–2.17). Higher post-first tumor psoralen + ultraviolet A treatment rates also increased risk (hazard ratio 1.24 for every additional 10 treatments per year, 95% confidence interval 1.06–1.47). Psoralen + ultraviolet A-treated psoriasis patients appear to have a greatly increased incidence of second squamous cell carcinoma compared with the general population. Patients who develop a squamous cell carcinoma after starting psoralen + ultraviolet A therapy should be closely monitored for a subsequent squamous cell carcinoma

Hippocampus and retrosplenial cortex combine path integration signals for successful navigation

The current study used fMRI in humans to examine goal-directed navigation in an open field environment. We designed a task that required participants to encode survey-level spatial information and subsequently navigate to a goal location in either first person, third person, or survey perspectives. Critically, no distinguishing landmarks or goal location markers were present in the environment, thereby requiring participants to rely on path integration mechanisms for successful navigation. We focused our analysis on mechanisms related to navigation and mechanisms tracking linear distance to the goal location. Successful navigation required translation of encoded survey-level map information for orientation and implementation of a planned route to the goal. Our results demonstrate that successful first and third person navigation trials recruited the anterior hippocampus more than trials when the goal location was not successfully reached. When examining only successful trials, the retrosplenial and posterior parietal cortices were recruited for goal-directed navigation in both first person and third person perspectives. Unique to first person perspective navigation, the hippocampus was recruited to path integrate self-motion cues with location computations toward the goal location. Last, our results demonstrate that the hippocampus supports goal-directed navigation by actively tracking proximity to the goal throughout navigation. When using path integration mechanisms in first person and third person perspective navigation, the posterior hippocampus was more strongly recruited as participants approach the goal. These findings provide critical insight into the neural mechanisms by which we are able to use map-level representations of our environment to reach our navigational goals

Functional correlates of optic flow motion processing in Parkinson’s disease

The visual input created by the relative motion between an individual and the environment, also called optic flow, influences the sense of self-motion, postural orientation, veering of gait, and visuospatial cognition. An optic flow network comprising visual motion areas V6, V3A, and MT+, as well as visuo-vestibular areas including posterior insula vestibular cortex (PIVC) and cingulate sulcus visual area (CSv), has been described as uniquely selective for parsing egomotion depth cues in humans. Individuals with Parkinson’s disease (PD) have known behavioral deficits in optic flow perception and visuospatial cognition compared to age- and education-matched control adults (MC). The present study used functional magnetic resonance imaging (fMRI) to investigate neural correlates related to impaired optic flow perception in PD. We conducted fMRI on 40 non-demented participants (23 PD and 17 MC) during passive viewing of simulated optic flow motion and random motion. We hypothesized that compared to the MC group, PD participants would show abnormal neural activity in regions comprising this optic flow network. MC participants showed robust activation across all regions in the optic flow network, consistent with studies in young adults, suggesting intact optic flow perception at the neural level in healthy aging. PD participants showed diminished activity compared to MC particularly within visual motion area MT+ and the visuo-vestibular region CSv. Further, activation in visuo-vestibular region CSv was associated with disease severity. These findings suggest that behavioral reports of impaired optic flow perception and visuospatial performance may be a result of impaired neural processing within visual motion and visuo-vestibular regions in PD.Published versio

Headache and Acute Illness in Children

Thirty-seven children with headaches who were seen in a walk-in clinic were matched to 37 headache-free controls. Thirty percent of the headache group and 11% of the headache-free control group had a body temperature above 38°C (p < 0.05). Nonrhythmic pain was more commonly associated with fever than was rhythmic pain (p < 0.05). Of 34 headache subjects who completed questionnaires, those with more intense headaches reported a greater number of headache-exacerbating factors (p < 0.01).Bilateral headaches were more painful than unilateral headaches, and in two thirds of the subjects, the intensity of pain paralleled the course of the underlying illness. A family history of migraine was more common in the headache group as compared to the headache-free control group (p < 0.05). Headaches associated with acute illnesses may be a precursor to later migraine. (J Child Neurol 1987;2:22-27)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68022/2/10.1177_088307388700200104.pd

CO J=2-1 line emission in cluster galaxies at z~1: fueling star formation in dense environments

We present observations of CO J=2-1 line emission in infrared-luminous cluster galaxies at z~1 using the IRAM Plateau de Bure Interferometer. Our two primary targets are optically faint, dust-obscured galaxies (DOGs) found to lie within 2 Mpc of the centers of two massive (>10^14 Msun) galaxy clusters. CO line emission is not detected in either DOG. We calculate 3-sigma upper limits to the CO J=2-1 line luminosities, L'_CO < 6.08x10^9 and < 6.63x10^9 K km/s pc^2. Assuming a CO-to-H_2 conversion factor derived for ultraluminous infrared galaxies in the local Universe, this translates to limits on the cold molecular gas mass of M_H_2 < 4.86x10^9 Msun and M_H_2 < 5.30x10^9 Msun. Both DOGs exhibit mid-infrared continuum emission that follows a power-law, suggesting that an AGN contributes to the dust heating. As such, estimates of the star formation efficiencies in these DOGs are uncertain. A third cluster member with an infrared luminosity, L_IR < 7.4x10^11 Lsun, is serendipitously detected in CO J=2-1 line emission in the field of one of the DOGs located roughly two virial radii away from the cluster center. The optical spectrum of this object suggests that it is likely an obscured AGN, and the measured CO line luminosity is L'_CO = (1.94 +/- 0.35)x10^10 K km/s pc^2, which leads to an estimated cold molecular gas mass M_H_2 = (1.55+/-0.28)x10^10 Msun. A significant reservoir of molecular gas in a z~1 galaxy located away from the cluster center demonstrates that the fuel can exist to drive an increase in star-formation and AGN activity at the outskirts of high-redshift clusters.Comment: 22 pages, 4 figures; accepted for publication in Ap