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  • The anatomy of apathy: A neurocognitive framework for amotivated behaviour.

    3 July 2018

    Apathy is a debilitating syndrome associated with many neurological disorders, including several common neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, and focal lesion syndromes such as stroke. Here, we review neuroimaging studies to identify anatomical correlates of apathy, across brain disorders. Our analysis reveals that apathy is strongly associated with disruption particularly of dorsal anterior cingulate cortex (dACC), ventral striatum (VS) and connected brain regions. Remarkably, these changes are consistent across clinical disorders and imaging modalities. Review of the neuroimaging findings allows us to develop a neurocognitive framework to consider potential mechanisms underlying apathy. According to this perspective, an interconnected group of brain regions - with dACC and VS at its core - plays a crucial role in normal motivated behaviour. Specifically we argue that motivated behaviour requires a willingness to work, to keep working, and to learn what is worth working for. We propose that deficits in any one or more of these processes can lead to the clinical syndrome of apathy, and outline specific approaches to test this hypothesis. A richer neurobiological understanding of the mechanisms underlying apathy should ultimately facilitate development of effective therapies for this disabling condition.

  • Subthalamic nucleus gamma activity increases not only during movement but also during movement inhibition.

    8 August 2018

    Gamma activity in the subthalamic nucleus (STN) is widely viewed as a pro-kinetic rhythm. Here we test the hypothesis that rather than being specifically linked to movement execution, gamma activity reflects dynamic processing in this nucleus. We investigated the role of gamma during fast stopping and recorded scalp electroencephalogram and local field potentials from deep brain stimulation electrodes in 9 Parkinson's disease patients. Patients interrupted finger tapping (paced by a metronome) in response to a stop-signal sound, which was timed such that successful stopping would occur only in ~50% of all trials. STN gamma (60-90 Hz) increased most strongly when the tap was successfully stopped, whereas phase-based connectivity between the contralateral STN and motor cortex decreased. Beta or theta power seemed less directly related to stopping. In summary, STN gamma activity may support flexible motor control as it did not only increase during movement execution but also during rapid action-stopping.

  • Multifocal versus monofocal intraocular lenses after cataract extraction.

    3 July 2018

    BACKGROUND: Good unaided distance visual acuity (VA) is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: To assess the visual effects of multifocal IOLs in comparison with the current standard treatment of monofocal lens implantation. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), the ISRCTN registry (, (, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) ( We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. We also considered trials comparing multifocal IOLs with "monovision" whereby one eye is corrected for distance vision and one eye corrected for near vision. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed the 'certainty' of the evidence using GRADE. MAIN RESULTS: We found 20 eligible trials that enrolled 2230 people with data available on 2061 people (3194 eyes). These trials were conducted in Europe (13), China (three), USA (one), Middle East (one), India (one) and one multicentre study in Europe and the USA. Most of these trials compared multifocal with monofocal lenses; two trials compared multifocal lenses with monovision. There was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask participants and outcome assessors. It was also difficult to assess the role of reporting bias.There was moderate-certainty evidence that the distance acuity achieved with multifocal lenses was not different to that achieved with monofocal lenses (unaided VA worse than 6/6: pooled RR 0.96, 95% confidence interval (CI) 0.89 to 1.03; eyes = 682; studies = 8). People receiving multifocal lenses may achieve better near vision (RR for unaided near VA worse than J3/J4 was 0.20, 95% CI 0.07 to 0.58; eyes = 782; studies = 8). We judged this to be low-certainty evidence because of risk of bias in the included studies and high heterogeneity (I2 = 93%) although all included studies favoured multifocal lenses with respect to this outcome.People receiving multifocal lenses may be less spectacle dependent (RR 0.63, 95% CI 0.55 to 0.73; eyes = 1000; studies = 10). We judged this to be low-certainty evidence because of risk of bias and evidence of publication bias (skewed funnel plot). There was also high heterogeneity (I2 = 67%) but all studies favoured multifocal lenses. We did not additionally downgrade for this.Adverse subjective visual phenomena were more prevalent and more troublesome in participants with a multifocal IOL compared with monofocals (RR for glare 1.41, 95% CI 1.03 to 1.93; eyes = 544; studies = 7, low-certainty evidence and RR for haloes 3.58, 95% CI 1.99 to 6.46; eyes = 662; studies = 7; moderate-certainty evidence).Two studies compared multifocal lenses with monovision. There was no evidence for any important differences in distance VA between the groups (mean difference (MD) 0.02 logMAR, 95% CI -0.02 to 0.06; eyes = 186; studies = 1), unaided intermediate VA (MD 0.07 logMAR, 95% CI 0.04 to 0.10; eyes = 181; studies = 1) and unaided near VA (MD -0.04, 95% CI -0.08 to 0.00; eyes = 186; studies = 1) compared with people receiving monovision. People receiving multifocal lenses were less likely to be spectacle dependent (RR 0.40, 95% CI 0.30 to 0.53; eyes = 262; studies = 2) but more likely to report problems with glare (RR 1.41, 95% CI 1.14 to 1.73; eyes = 187; studies = 1) compared with people receiving monovision. In one study, the investigators noted that more people in the multifocal group underwent IOL exchange in the first year after surgery (6 participants with multifocal vs 0 participants with monovision). AUTHORS' CONCLUSIONS: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs although there is uncertainty as to the size of the effect. Whether that improvement outweighs the adverse effects of multifocal IOLs, such as glare and haloes, will vary between people. Motivation to achieve spectacle independence is likely to be the deciding factor.

  • Early treatment of acute submacular haemorrhage secondary to wet AMD using intravitreal tissue plasminogen activator, C3F8, and an anti-VEGF agent.

    3 July 2018

    PurposeAcute submacular haemorrhage secondary to wet age-related macular degeneration (AMD) has a poor prognosis for which there is currently no 'gold standard' treatment. We evaluated the efficacy of early treatment using intravitreal triple therapy of tissue plasminogen activator (tPA), expansile gas, and an anti-VEGF agent.MethodsThis retrospective case series included eight patients presenting with acute submacular haemorrhage involving the fovea. All patients received treatment with 50 μg (0.05 ml) tPA, 0.3 ml 100% perfluoropropane (C3F8), and an anti-VEGF agent (0.05 mg Ranibizumab or 1.25 mg Bevacizumab in 0.05 ml) administered via intravitreal injection. An anterior chamber paracentesis post injection or vitreous tap was performed before injection to prevent retinal vascular occlusion secondary to raised intra-ocular pressure. Outcomes assessed were visual acuity, change in macular morphology, and complications.ResultsPatients presented promptly with delay between symptom onset and clinic review being 1.9±0.6 days (mean±SD). Treatment was delivered quickly with interval from presentation to treatment being 1.1±1.2 days. Symptom onset to treatment was 3.0±1.0 days. Subfoveal haemorrhage was effectively displaced in all patients. LogMAR visual acuity improved from 1.67±0.47 at presentation to 0.63±0.33 at final follow-up (P<0.0001), a mean of 7.9±4.8 months after treatment. Central retinal thickness improved from 658.1±174.2 μm at presentation to 316.6±142.4 μm at final follow-up (P=0.0028).ConclusionsEarly treatment of submacular haemorrhage using intravitreal tPA, C3F8, and anti-VEGF was effective in significantly improving visual acuity in this series of patients who presented soon after symptom onset. Treatment was well tolerated in this group of elderly and potentially frail patients.

  • Idiopathic choroidal neovascularisation in pregnancy: treatment options and a successful outcome.

    3 July 2018

    Choroidal neovascularisation (CNV) is a major cause of visual loss and treatment options aim to halt progression and stabilise vision. We describe a 29-year-old woman who presented with blurred vision and distortion in her left eye while 26 weeks pregnant. She was diagnosed with idiopathic CNV and multiple treatment options were discussed. The patient did not want to undertake any risks from having an anti vascular endothelial growth factor agent during pregnancy. Therefore on discussion with the obstetric team, she elected to have early delivery at 32 weeks followed by a course of intravitreal bevacizumab. Subsequently there was resolution of symptoms and intraretinal and subretinal fluid. CNV is uncommonly seen in pregnancy and there remains no consensus on treatment. We describe the third reported case of idiopathic CNV in pregnancy. Careful patient counselling and close liaison between the ophthalmology and obstetric teams are necessary in this condition to obtain a safe outcome while maximising vision.

  • Temporal alignment of anticipatory motor cortical beta lateralisation in hidden visual-motor sequences.

    3 July 2018

    Performance improves when participants respond to events that are structured in repeating sequences, suggesting that learning can lead to proactive anticipatory preparation. Whereas most sequence-learning studies have emphasised spatial structure, most sequences also contain a prominent temporal structure. We used MEG to investigate spatial and temporal anticipatory neural dynamics in a modified serial reaction time (SRT) task. Performance and brain activity were compared between blocks with learned spatial-temporal sequences and blocks with new sequences. After confirming a strong behavioural benefit of spatial-temporal predictability, we show lateralisation of beta oscillations in anticipation of the response associated with the upcoming target location and show that this also aligns to the expected timing of these forthcoming events. This effect was found both when comparing between repeated (learned) and new (unlearned) sequences, as well as when comparing targets that were expected after short vs. long intervals within the repeated (learned) sequence. Our findings suggest that learning of spatial-temporal structure leads to proactive and dynamic modulation of motor cortical excitability in anticipation of both the location and timing of events that are relevant to guide action.