Blue emitting exciplex for yellow and white organic light-emitting diodes.

White organic light-emitting diodes (WOLEDs) have several desirable features, but their commercialization is hindered by the poor stability of blue light emitters and high production costs due to complicated device structures. Herein, we investigate a standard blue emitting hole transporting material (HTM) N,N'-bis(naphthalen-1-yl)-N,N'-bis(phenyl)benzidine (NPB) and its exciplex emission upon combining with a suitable electron transporting material (ETM), 3-(biphenyl-4-yl)-5-(4-tert-butylphenyl)-4-phenyl-4H-1,2,4-triazole (TAZ). Blue and yellow OLEDs with simple device structures are developed by using a blend layer, NPB:TAZ, as a blue emitter as well as a host for yellow phosphorescent dopant iridium (III) bis(4-phenylthieno[3,2-c]pyridinato-N,C2')acetylacetonate (PO-01). Strategic device design then exploits the ambipolar charge transport properties of tetracene as a spacer layer to connect these blue and yellow emitting units. The tetracene-linked device demonstrates more promising results compared to those using a conventional charge generation layer (CGL). Judicious choice of the spacer prevents exciton diffusion from the blue emitter unit, yet facilitates charge carrier transport to the yellow emitter unit to enable additional exciplex formation. This complementary behavior of the spacer improves the blue emission properties concomitantly yielding reasonable yellow emission. The overall white light emission properties are enhanced, achieving CIE coordinates (0.36, 0.39) and color temperature (4643 K) similar to daylight. Employing intermolecular exciplex emission in OLEDs simplifies the device architecture via its dual functionality as a host and as an emitter.

Large area inkjet-printed OLED fabrication with solution-processed TADF ink.

This work demonstrates successful large area inkjet printing of a thermally activated delayed fluorescence (TADF) material as the emitting layer of organic light-emitting diodes (OLEDs). TADF materials enable efficient light emission without relying on heavy metals such as platinum or iridium. However, low-cost manufacturing of large-scale TADF OLEDs has been restricted due to their incompatibility with solution processing techniques. In this study, we develop ink formulation for a TADF material and show successful ink jet printing of intricate patterns over a large area (6400 mm2) without the use of any lithography. The stable ink is successfully achieved using a non-chlorinated binary solvent mixture for a solution processable TADF material, 3-(9,9-dimethylacridin-10(9H)-yl)-9H-xanthen-9-one dispersed in 4,4'-bis-(N-carbazolyl)-1,1'-biphenyl host. Using this ink, large area ink jet printed OLEDs with performance comparable to the control spin coated OLEDs are successfully achieved. In this work, we also show the impact of ink viscosity, density, and surface tension on the droplet formation and film quality as well as its potential for large-area roll-to-roll printing on a flexible substrate. The results represent a major step towards the use of TADF materials for large-area OLEDs without employing any lithography.

Quality of life implications for elevated trait impulsivity in people with Parkinson's disease.

BACKGROUND: Several non-motor features of Parkinson's disease (PD) are known to adversely affect patient health-related quality of life (HRQL). However, the specific impact of neuropsychiatric complications, such as impulsive behaviour, is yet to be elucidated. OBJECTIVES: The present cross-sectional, observational study aimed to investigate the effects of heightened trait impulsivity on HRQL in individuals with PD. METHODS: A total of 322 people with idiopathic PD were sequentially recruited from Movement Disorder clinics across Australia. Trait impulsivity in patients was determined by Barratt's Impulsiveness Scale Version 11 (BIS-11), and grouped into tertiles (low, medium, and high). Patient HRQL was determined by the 39-item Parkinson's Disease Questionnaire (PDQ-39), complemented by the Cambridge Behavioural Inventory-Revised (CBI-R) indicating caregivers' perception of patient HRQL. RESULTS: When total BIS-11 scores were grouped into tertiles, patient perceived and caregiver-perceived HRQL were 1.7-fold (p < .001) and 2.2-fold (p < .001) worse in the high BIS-11 group when compared to patients in the low group. Univariate analysis revealed significant associations between second-order attentional (p < .001) and non-planning (p < .001) impulsivity domains with PDQ-39 scores. When controlling for confounding demographic and clinical variables, a multivariate linear regression model revealed second-order attentional impulsivity was independently predictive of poor patient perceived HRQL (p < .001). CONCLUSION: These findings suggest that increasing trait impulsivity is significantly associated with patient perceived HRQL in PD. Improved knowledge and recognition of subclinical impulsivity may guide clinicians' treatment and reduce disease burden for patients experiencing PD symptoms.

Amplified Spontaneous Emission from Zwitterionic Excited-State Intramolecular Proton Transfer.

The unique four-level photocycle characteristics of excited-state intramolecular proton transfer (ESIPT) materials enable population inversion and large spectral separation between absorption and emission through their respective enol and keto forms. This leads to minimal or no self-absorption losses, a favorable feature in acting as an optical gain medium. While conventional ESIPT materials with an enol-keto tautomerism process are widely known, zwitterionic ESIPT materials, particularly those with high photoluminescence, are scarce. Facilitated by the synthesis and characterization of a new family of 2-hydroxyphenyl benzothiazole (HBT) with fluorene substituents, HBT-Fl1 and HBT-Fl2, we herein report the first efficient zwitterionic ESIPT lasing material (HBT-Fl2). The zwitterionic ESIPT HBT-Fl2 not only shows a remarkably low solid-state amplified spontaneous emission (ASE) threshold of 5.3 µJ/cm2 with an ASE peak at 609 nm but also exhibits high ASE photostability. Coupled with its substantially large Stokes shift (≈236 nm ≈10,390 cm-1) and an extremely small overlap of excited-state absorption with ASE emission, comprehensive density functional theory (DFT) and time-dependent DFT studies reveal the zwitterionic characteristics of HBT-Fl2. In opposition to conventional ESIPT with π-delocalized tautomerism as observed in analogue HBT-Fl1 and parent HBT, HBT-Fl2 instead shows charge redistribution in the proton transfer through the fluorene conjugation. This structural motif provides a design tactic in the innovation of new zwitterionic ESIPT materials for efficient light amplification in red and longer-wavelength emission.

Cibalackrot Dendrimers for Hyperfluorescent Organic Light-Emitting Diodes.

Hyperfluorescent organic light-emitting diodes (HF-OLEDs) enable a cascading Förster resonance energy transfer (FRET) from a suitable thermally activated delayed fluorescent (TADF) assistant host to a fluorescent end-emitter to give efficient OLEDs with relatively narrowed electroluminescence compared to TADF-OLEDs. Efficient HF-OLEDs require optimal FRET with minimum triplet diffusion via Dexter-type energy transfer (DET) from the TADF assistant host to the fluorescent end-emitter. To hinder DET, steric protection of the end-emitters has been proposed to disrupt triplet energy transfer. In this work, the first HF-OLEDs based on structurally well-defined macromolecules, dendrimers is reported. The dendrimers contain new highly twisted dendrons attached to a Cibalackrot core, resulting in high solubility in organic solvents. HF-OLEDs based on dendrimer blend films are fabricated to show external quantum efficiencies of >10% at 100 cd m-2 . Importantly, dendronization with the bulky dendrons is found to have no negative impact to the FRET efficiency, indicating the excellent potential of the dendritic macromolecular motifs for HF-OLEDs. To fully prevent the undesired triplet diffusion, Cibalackrot dendrimers HF-OLEDs are expected to be further improved by adding additional dendrons to the Cibalackrot core and/or increasing dendrimer generations.

Low Light Amplification Threshold and Reduced Efficiency Roll-Off in Thick Emissive Layer OLEDs from a Diketopyrrolopyrrole Derivative.

External quantum efficiency (EQE) roll-off under high current injection has been one of the major limiting factors toward the development of organic semiconductor laser diodes (OSLDs). While significant progress in this regard has been made on organic semiconductors (OSCs) emitting in the blue-green region of the visible spectrum, OSCs with longer wavelength emission (>600 nm) have fallen behind in both material development and the advancement in device architectures suitable for the realization of OSLDs. Therefore, to make simultaneous incremental advancements, a host-guest system comprising of a high performing poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) polymer and an efficient small molecule laser dye, dithiophenyl diketopyrrolopyrrole (DT-DPP), is used. This combination provides an extremely low amplified spontaneous emission threshold of 4.2 µJ cm-2 at an emission wavelength of 620 nm. The solution-processed organic light-emitting diodes (OLEDs) fabricated using this system exhibit a high external quantum efficiency (EQE) of 2.6% with low efficiency roll-off and high current injection up to 90 A cm-2 to yield ultrahigh luminance of over 1.5 million cd m-2 .

Probing polaron-induced exciton quenching in TADF based organic light-emitting diodes.

Polaron-induced exciton quenching in thermally activated delayed fluorescence (TADF)-based organic light-emitting diodes (OLEDs) can lead to external quantum efficiency (EQE) roll-off and device degradation. In this study, singlet-polaron annihilation (SPA) and triplet-polaron annihilation (TPA) were investigated under steady-state conditions and their relative contributions to EQE roll-off were quantified, using experimentally obtained parameters. It is observed that both TPA and SPA can lead to efficiency roll-off in 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN) doped OLEDs. Charge imbalance and singlet-triplet annihilation (STA) were found to be the main contributing factors, whereas the device degradation process is mainly dominated by TPA. It is also shown that the impact of electric field-induced exciton dissociation is negligible under the DC operation regime (electric field < 0.5 MV cm-1). Through theoretical simulation, it is demonstrated that improvement to the charge recombination rate may reduce the effect of polaron-induced quenching, and thus significantly decrease the EQE roll-off.

Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson's Disease Cohort.

Background: There has been increasing recognition of the importance of the gut microbiome in Parkinson's disease (PD), but the influence of geographic location has received little attention. The present study characterized the gut microbiota and associated changes in host metabolic pathways in an Australian cohort of people with PD (PwP). Methods: The study involved recruitment and assessment of 87 PwP from multiple Movement Disorders Clinics in Australia and 47 healthy controls. Illumina sequencing of the V3 and V4 regions of the 16S rRNA gene was used to distinguish inter-cohort differences in gut microbiota; KEGG analysis was subsequently performed to predict functional changes in host metabolic pathways. Results: The current findings identified significant differences in relative abundance and diversity of microbial operational taxonomic units (OTUs), and specific bacterial taxa between PwP and control groups. Alpha diversity was significantly reduced in PwP when compared to controls. Differences were found in two phyla (Synergistetes and Proteobacteria; both increased in PwP), and five genera (Colidextribacter, Intestinibacter, Kineothrix, Agathobaculum, and Roseburia; all decreased in PwP). Within the PD cohort, there was no association identified between microbial composition and gender, constipation or use of gastrointestinal medication. Furthermore, KEGG analysis identified 15 upregulated and 11 downregulated metabolic pathways which were predicted to be significantly altered in PwP. Conclusion: This study provides the first comprehensive characterization of the gut microbiome and predicted functional metabolic effects in a southern hemisphere PD population, further exploring the possible mechanisms whereby the gut microbiota may exert their influence on this disease, and providing evidence for the incorporation of such data in future individualized therapeutic strategies.

Elevated HDL Levels Linked to Poorer Cognitive Ability in Females With Parkinson's Disease.

INTRODUCTION: Cholesterol levels have been associated with age-related cognitive decline, however, such an association has not been comprehensively explored in people with Parkinson's disease (PD). To address this uncertainty, the current cross-sectional study examined the cholesterol profile and cognitive performance in a cohort of PD patients. METHODS: Cognitive function was evaluated using two validated assessments (ACE-R and SCOPA-COG) in 182 people with PD from the Australian Parkinson's Disease Registry. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and Triglyceride (TRG) levels were examined within this cohort. The influence of individual lipid subfractions on domain-specific cognitive performance was investigated using covariate-adjusted generalised linear models. RESULTS: Females with PD exhibited significantly higher lipid subfraction levels (TC, HDL, and LDL) when compared to male counterparts. While accounting for covariates, HDL levels were strongly associated with poorer performance across multiple cognitive domains in females but not males. Conversely, TC and LDL levels were not associated with cognitive status in people with PD. CONCLUSION: Higher serum HDL associates with poorer cognitive function in females with PD and presents a sex-specific biomarker for cognitive impairment in PD.

Tunable Light-Emission Properties of Solution-Processable N-Heterocyclic Carbene Cyclometalated Gold(III) Complexes for Organic Light-Emitting Diodes.

N-Heterocyclic carbene (NHC) cyclometalated gold(III) complexes remain very scarce and therefore their photophysical properties remain currently underexplored. Moreover, gold(III) complexes emitting in the blue region of the electromagnetic spectrum are rare. In this work, a series of four phosphorescent gold(III) complexes was investigated bearing four different NHC monocyclometalated (C^C*)-type ligands and a dianionic (N^N)-type ancillary ligand ((N^N)=5,5'-(propane-2,2-diyl)bis(3-(trifluoromethyl)-1 H-pyrazole) (mepzH2 )). The complexes exhibit strong phosphorescence when doped in poly(methyl methacrylate) (PMMA) at room temperature, which were systematically tuned from sky-blue [λPL =456 nm, CIE coordinates: (0.20, 034)] to green [λPL =516 nm, CIE coordinates: (0.31, 0.54)] by varying the monocyclometalated (C^C*) ligand framework. The complexes revealed high quantum efficiencies (ϕPL ) of up to 43 % and excited-state lifetimes (τ0 ) between 15-266 µs. The radiative rate constant values found for these complexes (kr =103 -104  s-1 ) are the highest found in comparison to previously known best-performing monocyclometalated gold(III) complexes. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations of these complexes further lend support to the excited-state nature of these complexes. The calculations showed a significant contribution of the gold(III) metal center in the lowest unoccupied molecular orbitals (LUMOs) of up to 18 %, which was found to be unique for this class of cyclometalated gold(III) complexes. Additionally, organic light-emitting diodes (OLEDs) were fabricated by using a solution process to provide the first insight into the electroluminescent (EL) properties of this new class of gold(III) complexes.

Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson's disease.

BACKGROUND: Cognitive impairment is an important and diverse symptom of Parkinson's disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been comprehensively investigated. OBJECTIVES: This cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large PD cohort. METHODS: Cognitive function was evaluated using the Addenbrooke's Cognitive Examination in 392 people with PD (PwP) from the Australian Parkinson's Disease Registry. The influence of sex on domain-specific cognitive performance was investigated using covariate-corrected generalised linear models. In a repeated measures longitudinal subset of 127 PwP, linear mixed models were used to assess the impact of sex on cognition over time, while accounting for covariates. RESULTS: Cross-sectional-corrected modelling revealed that sex was significantly predictive of cognitive performance, with males performing worse than females on global cognition, and memory and fluency domains. Longitudinally, sex was significantly predictive of cognitive decline, with males exhibiting a greater reduction in global cognition and language, whereas females showed a greater decline in attention/orientation, memory and visuospatial domains, despite starting with higher baseline scores. At follow-up, a significantly higher proportion of males than females fulfilled criteria for mild cognitive impairment or PD dementia. CONCLUSIONS: Sex was revealed as a significant determinant of overall cognitive performance as well as specific cognitive domains, with a differential pattern of decline in male and female participants. Such sex-specific findings appear to explain some of the heterogeneity observed in PD, warranting further investigation of mechanisms underlying this sexual dimorphism.

Elevated Serum Ceruloplasmin Levels Are Associated with Higher Impulsivity in People with Parkinson's Disease.

BACKGROUND: Heightened impulsivity has been reported in a subset of people with Parkinson's disease (PwP) and is considered a risk factor for the development of impulse control disorders (ICDs). However, at present, there are no recognised biochemical markers of heightened impulsivity. OBJECTIVES: To determine if ceruloplasmin, a serum marker involved in the regulation of iron and copper homeostasis, is associated with trait impulsivity in PwP. METHODS: The study measured serum ceruloplasmin and impulsivity using the Barratt Impulsiveness Scale (BIS-11) in an Australian cohort of 214 PwP. Multivariate general linear models (GLMs) were used to identify whether higher serum ceruloplasmin levels (>75th percentile) were significantly predictive of BIS-11 scores. RESULTS: Serum ceruloplasmin was higher in females with PD (p < 0.001) and associated with MDS-UPDRS III, Hoehn and Yahr, and ACE-R scores (p < 0.05). When correcting for covariates, higher serum ceruloplasmin concentrations were associated with the 2nd order nonplanning impulsivity and with the 1st order self-control and cognitive complexity impulsivity domains. CONCLUSIONS: Higher serum ceruloplasmin levels are independently associated with heightened nonplanning impulsivity in PwP. Thus, serum ceruloplasmin levels may have clinical utility as a marker for heightened impulsivity in PD.

The Latent-Variable Structure of the Addenbrooke's Cognitive Examination-Revised.

OBJECTIVES: To establish a theoretically justified factor structure for the Addenbrooke's Cognitive Examination-Revised (ACE-R). METHODS: Our sample comprised 288 patients with Parkinson's disease (179 men and 109 women). The mean age of participants was 66.66 (SD = 8.93). Confirmatory factor analysis (CFA) was used to evaluate the test developers' five-factor model of the ACE-R, and alternative models as guided by the Cattell-Horn-Carroll (CHC) theory. Exploratory structural equation modeling (ESEM) was also employed to examine alternative factor structures to ensure that a good candidate model was not overlooked. RESULTS: A three-factor CHC-guided CFA and a similar three-factor ESEM model both showed acceptable overall fit, and interpretable factor structures. The three-factor CFA model showed two factors of pure CHC constructs: acquired knowledge (Gc), and visuospatial ability (Gv), and one combined factor, namely, long-term memory retrieval, fluency, and working memory (Glr-Gsm). The three-factor ESEM model showed three factors essentially in line with the CFA results. CONCLUSION: The three-factor CHC-guided CFA model was selected as the best model to guide clinical interpretation of cognitive variables underlying ACE-R scores.

Trait Impulsivity Is Independent of Mild Cognitive Impairment in a Parkinson's Disease Cohort.

INTRODUCTION: Patients with Parkinson's disease (PD) commonly experience cognitive deficits and some also develop impulse control disorders (ICDs); however, the relationship between impulsivity and cognitive dysfunction remains unclear. This study investigated whether trait impulsivity associates with mild cognitive impairment (MCI), or is altered in a PD patient cohort with MCI. METHODS: A total of 302 patients with idiopathic PD were recruited sequentially from three Australian Movement Disorder clinics. Based on cognitive scores, participants were divided into two groups, one defined as having mild cognitive impairment (PD-MCI; n = 113) and the other with normal cognitive function (PD-C; n = 189). Trait impulsivity was evaluated using the Barrett Impulsiveness Scale 11 (BIS-11). Total impulsivity scores, as well as subscale scores, were compared between PD-C and PD-MCI groups. RESULTS: The PD-MCI cohort had significantly lower scores in all cognitive domains, and mirrored expected clinical differences in medication, motor symptoms, and disease duration, when compared to the PD-C cohort. Self-reported impulsivity was not significantly different between groups, nor was there a difference within first-order subscale scores: attention (p=0.137), cognitive instability (p=0.787), self-control (p=0.503), cognitive complexity (p=0.157), motor impulsivity (p=0.559), or perseverance (p=0.734) between the PD-MCI and PD-C groups. CONCLUSIONS: These findings suggest that impulsive traits and behaviors are independent of changes in cognitive state and are not altered in PD patients with mild cognitive impairment.

Elevated Serum Homocysteine Levels Have Differential Gender-Specific Associations with Motor and Cognitive States in Parkinson's Disease.

BACKGROUND: Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson's disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. METHODS: Serum homocysteine, folate, and vitamin B12 levels were measured in 205 people with PD and 78 age-matched healthy controls. People with Parkinson's disease underwent a battery of clinical assessments to evaluate symptom severity, including motor (MDS-UPDRS) and cognitive (ACE-R) assessments. Multivariate generalised linear models were created, controlling for confounding variables, and were used to determine whether serum markers are associated with various symptom outcome measures. RESULTS: People with Parkinson's disease displayed significantly elevated homocysteine levels (p < 0.001), but not folate or vitamin B12 levels, when compared to healthy controls. A significant positive correlation between homocysteine and MDS-UPDRS III score was identified in males with Parkinson's disease (r s = 0.319, p < 0.001), but not in females, whereas a significant negative correlation between homocysteine levels and total ACE-R score was observed in females with Parkinson's disease (r s = -0.449, p < 0.001), but not in males. Multivariate general linear models confirmed that homocysteine was significantly predictive of MDS-UPDRS III score in male patients (p=0.004) and predictive of total ACE-R score in female patients (p=0.021). CONCLUSION: Elevated serum homocysteine levels are associated with a greater motor impairment in males with Parkinson's disease and poorer cognitive performance in females with Parkinson's disease. Our gender-specific findings may help to explain previous discrepancies in the literature surrounding the utility of homocysteine as a biomarker in PD.

Objective measurement in routine care of people with Parkinson's disease improves outcomes.

It is common in medicine to titrate therapy according to target ranges of objectively measured parameters. Objective measurement of motor function is available for Parkinson's Disease (PD), making it possible to optimise therapy and clinical outcomes. In this study, an accelerometry based measurement and predefined target ranges were used to assess motor function in a Northern Tasmania PD cohort managed by a Movement Disorder clinic. Approximately 40% (n = 103) of the total PD population participated in this study and motor scores were within target in 22%. In the 78% above target, changes in oral therapy were recommended in 74%, Advanced Therapy in 12% and treatment was contraindicated in 9%. Following changes in oral therapy, there was a further objective measurement and clinical consultation to establish whether scores had reached target range: if so subjects left the study, otherwise further changes of therapy were recommended (unless contraindications were present). Seventy-seven cases completed the study, with 48% achieving target (including 22% at outset), Advanced Therapy recommended in 19% and contraindications preventing any change in therapy in 17%. In the 43% of cases in whom oral therapy was changed, total UPDRS improved significantly (effect size = 8) as did the PDQ39 in cases reaching target. NMS Quest and MOCA scores also improved significantly. This study shows that many people in a representative cohort of PD would benefit from objective assessment and treatment of their PD features against a target.

The use of accelerometry as a tool to measure disturbed nocturnal sleep in Parkinson's disease.

Sleep disturbances are common in Parkinson's disease (PD). We used the Parkinson's KinetiGraph (PKG), an objective movement recording system for PD to assess night time sleep in 155 people aged over 60 and without PD (controls), 72 people with PD (PwP) and 46 subjects undergoing a Polysomnogram (PSG: 36 with sleep disorder and 10 with normal sleep). The PKG system uses a wrist worn logger to capture acceleration and derive a bradykinesia score (BKS) every 2 min over 6 days. The BKS ranges from 0-160 with higher scores associated with lesser mobility. Previously we showed that BKS > 80 were associated with day time sleep and used this to produce scores for night time sleep: Efficiency (Percent time with BKS > 80), Fragmentation (Average duration of runs of BKS > 80) and Sleep Quality (BKS > 111 as a representation of atonia). There was a fair association with BKS score and sleep level as judged by PSG. Using these PKG scores, it was possible to distinguish between normal and abnormal PSG studies with good Selectivity (86%) and Sensitivity (80%). The PKG's sleep scores were significantly different in PD and Controls and correlated with a subject's self-assessment (PDSS 2) of the quality, wakefulness and restlessness. Using both the PDSS 2 and the PKG, it was apparent that sleep disturbances were apparent early in disease in many PD subjects and that subjects with poor night time sleep were more likely to have day time sleepiness. This system shows promise as a quantitative score for assessing sleep in Parkinson's disease.

An objective fluctuation score for Parkinson's disease.

INTRODUCTION: Establishing the presence and severity of fluctuations is important in managing Parkinson's Disease yet there is no reliable, objective means of doing this. In this study we have evaluated a Fluctuation Score derived from variations in dyskinesia and bradykinesia scores produced by an accelerometry based system. METHODS: The Fluctuation Score was produced by summing the interquartile range of bradykinesia scores and dyskinesia scores produced every 2 minutes between 0900-1800 for at least 6 days by the accelerometry based system and expressing it as an algorithm. RESULTS: This Score could distinguish between fluctuating and non-fluctuating patients with high sensitivity and selectivity and was significant lower following activation of deep brain stimulators. The scores following deep brain stimulation lay in a band just above the score separating fluctuators from non-fluctuators, suggesting a range representing adequate motor control. When compared with control subjects the score of newly diagnosed patients show a loss of fluctuation with onset of PD. The score was calculated in subjects whose duration of disease was known and this showed that newly diagnosed patients soon develop higher scores which either fall under or within the range representing adequate motor control or instead go on to develop more severe fluctuations. CONCLUSION: The Fluctuation Score described here promises to be a useful tool for identifying patients whose fluctuations are progressing and may require therapeutic changes. It also shows promise as a useful research tool. Further studies are required to more accurately identify therapeutic targets and ranges.

A conditioned response as a measure of impulsive-compulsive behaviours in Parkinson's disease.

OBJECTIVES: Parkinson's Disease patients wore a device on the wrist that gave reminders to take levodopa and also measured bradykinesia and dyskinesia. Consumption of medications was acknowledged by placing the thumb on the device. Some patients performed this acknowledgement repeatedly and unconsciously. This study examines whether this behaviour reflected increased impulsivity. METHODS AND RESULTS: Twenty five participants were selected because they had i) excess acknowledgements described above or ii) Impulsive-Compulsive Behaviours or iii) neither of these. A blinded assessor applied clinical scales to measure Impulsive-Compulsive Behaviours, cognition, depression, anxiety and apathy. A Response Ratio, representing the number of acknowledgements/number of doses (expressed as a percentage) was tightly correlated with ratings of Impulsive-Compulsive Behaviours (r²â€Š= 0.79) in 19/25 subjects. Some of these patients had dyskinesia, which was higher with extraneous responses than with response indicating medication consumption. Six of the 25 subjects had high Impulsive-Compulsive Behaviour Scores, higher apathy scores, low levels of dyskinesia and normal Response Ratios. Patients without ICB (low RR) also had low dyskinesia levels regardless of the relevance of the response. CONCLUSION: An elevated Response Ratio is a specific measure of a type of ICB where increased incentive salience is attributed to cues by the presence of high striatal dopamine levels, manifested by high levels of dyskinesia. This study also points to a second form of ICBs which occur in the absence of dyskinesia, has normal Response Ratios and higher apathy scores, and may represent prefrontal pathology.