Objective
Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide ...proof‐of‐principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.
Methods
We tested BCI‐controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale.
Results
Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation.
Interpretation
BCI‐controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Ann Neurol 2013;74:449–457
Adaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in ...contralateral hemibody Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and may be superior to conventional continuous DBS in Parkinson's disease (PD). We test whether potential benefits are retained with bilateral aDBS and in the face of concurrent medication.
We applied bilateral aDBS in 4 patients with PD undergoing DBS of the subthalamic nucleus. aDBS was delivered bilaterally with independent triggering of stimulation according to the amplitude of β activity at the corresponding electrode. Mean stimulation voltage was 3.0±0.1 volts. Motor assessments consisted of double-blinded video-taped motor UPDRS scores that included both limb and axial features.
UPDRS scores were 43% (p=0.04; Cohen's d=1.62) better with aDBS than without stimulation. Motor improvement with aDBS occurred despite an average time on stimulation (ToS) of only 45%. Levodopa was well tolerated during aDBS and led to further reductions in ToS.
Bilateral aDBS can improve both axial and limb symptoms and can track the need for stimulation across drug states.
Cancer, one of the world's leading causes of death today, remains almost absent relative to other pathological conditions, in the archaeological record, giving rise to the conclusion that the disease ...is mainly a product of modern living and increased longevity. This paper presents a male, young-adult individual from the archaeological site of Amara West in northern Sudan (c. 1200 BC) displaying multiple, mainly osteolytic, lesions on the vertebrae, ribs, sternum, clavicles, scapulae, pelvis, and humeral and femoral heads. Following radiographic, microscopic and scanning electron microscopic (SEM) imaging of the lesions, and a consideration of differential diagnoses, a diagnosis of metastatic carcinoma secondary to an unknown soft tissue cancer is suggested. This represents the earliest complete example in the world of a human who suffered metastatic cancer to date. The study further draws its strength from modern analytical techniques applied to differential diagnoses and the fact that it is firmly rooted within a well-documented archaeological and historical context, thus providing new insights into the history and antiquity of the disease as well as its underlying causes and progression.
Setup for MEG and intracranial recordings during Deep Brain Stimulation is described.Phantom experiment showed correct recovery of oscillatory sources despite artefacts.The method is applied to ...real data from a patient with Parkinson's Disease.Cortico-subthalamic coherence profiles on and off stimulation were comparable.
Deep Brain Stimulation (DBS) is an effective treatment for several neurological and psychiatric disorders. In order to gain insights into the therapeutic mechanisms of DBS and to advance future therapies a better understanding of the effects of DBS on large-scale brain networks is required.
In this paper, we describe an experimental protocol and analysis pipeline for simultaneously performing DBS and intracranial local field potential (LFP) recordings at a target brain region during concurrent magnetoencephalography (MEG) measurement. Firstly we describe a phantom setup that allowed us to precisely characterise the MEG artefacts that occurred during DBS at clinical settings.
Using the phantom recordings we demonstrate that with MEG beamforming it is possible to recover oscillatory activity synchronised to a reference channel, despite the presence of high amplitude artefacts evoked by DBS. Finally, we highlight the applicability of these methods by illustrating in a single patient with Parkinson's disease (PD), that changes in cortical-subthalamic nucleus coupling can be induced by DBS.
To our knowledge this paper provides the first technical description of a recording and analysis pipeline for combining simultaneous cortical recordings using MEG, with intracranial LFP recordings of a target brain nucleus during DBS.
Paints and plasters from two pharaonic settlement sites in Nubia (northern Sudan) were analysed to investigate the presence and origin of organic binding materials. The town of Sai was founded around ...the time of the pharaonic conquest of Kush (Upper Nubia) around 1500 BC, with Amara West created as a new centre for the pharaonic administration of the region around 1300 BC. Recent fieldwork at both sites yielded examples of paint palettes, including several from houses. These provide a different economic and social context to funerary contexts upon which most previous research has been conducted, making this study the first to report on binding media for vernacular architecture in the Nile Valley. It is also the first study of binding media from Nubia. Gas chromatography mass spectrometry (GC-MS) analysis of methanolysed and silylated paint and plaster samples revealed a range of monosaccharides present in eight of the seventeen samples from Amara West, and in six of the seven samples from Sai. Interpretation of the data was supported by field collection and study of locally available botanical gums. The results indicate that mixtures of gums were in use as a pigment binder at both sites during the mid- to late-second millennium BC. The possibility that some of these plant gums could have been imported from the Mediterranean is also posited.
Pigments from paint palettes and a grindstone excavated from the pharaonic town of Amara West (c. 1300–1050 BCE), which lies between the Second and Third Cataracts of the Nile, were examined using ...polarized light microscopy, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction, and scanning electron microscopy with energy dispersive X-ray spectroscopy. Most of the pigments were consistent with the typical ancient Egyptian palette, but the greens and some blues were unusual. Two types of green pigment were identified, chlorite (varieties clinochlore and penninite) and copper chloride hydroxide (atacamite type). The former constitutes a type of green earth which has only rarely been identified in pharaonic Egyptian contexts and may be more widespread than is currently reported. The majority of the blue pigment samples were Egyptian blue, but some were found to be a blue earth, the main component of which being sodic amphibole riebeckite. The use of this mineral as a pigment has not previously been reported in any Nile Valley context. These results prompt questions around local and potentially indigenous practices within an ancient colonial context, and highlight avenues for future research.
Bitumen has been identified for the first time in Egyptian occupied Nubia, from within the town of Amara West, occupied from around 1300 to 1050 BC. The bitumen can be sourced to the Dead Sea using ...biomarkers, evidencing a trade in this material from the eastern Mediterranean to Nubia in the New Kingdom or its immediate aftermath. Two different end uses for bitumen were determined at the site. Ground bitumen was identified in several paint palettes, and in one case can be shown to have been mixed with plant gum, which indicates the use of bitumen as a ground pigment. Bitumen was also identified as a component of a friable black solid excavated from a tomb, and a black substance applied to the surface of a painted and plastered coffin fragment. Both contained plant resin, indicating that this substance was probably applied as a ritual funerary liquid, a practice identified from this time period in Egypt. The use of this ritual, at a far remove from the royal Egyptian burial sites at Thebes, indicates the importance of this ritual as a component of the funeral, and the value attributed to the material components of the black liquid.
Egyptology has fared rather poorly on the internet. Sites of dubious scholarly value abound (some amusing: www.thepump.org), and though more reliable resources can be found through recognised Museum ...and University portals, these are often restricted to individual collections or projects. Turning to Karnak, the Centre Franco-Égyptien d'étude des temples de Karnak (CFEETK) has been responsible for excavations at the site since its formation in 1967, continuing the long history of French involvement at Karnak, going back through such luminaries as Henri Chevrier, Georges Legrain, Auguste Mariette and Gaston Maspero. The CFEETK has its own website (www.cfeetk.cnrs.fr), aimed at a more scholarly audience, with reports on field seasons available for download. Where does Digital Karnak sit within this online landscape? Three principal goals are set out for the project: (1) to assemble databases of information related to Karnak, (2) build an interactive computer model of the site, and (3) create a series of resources using the model and databases that are available online, primarily for undergraduate education.
Agricultural practices in northern Sudan have been changing rapidly but remain little documented. In this paper we aim to investigate changes to crops grown in living memory and their uses through ...interviews with Nubian farmers on the island of Ernetta. By exploring cultivation and crop processing practices, together with associated material culture and foodstuffs, we also seek to explore how agricultural and food heritage are connected, and to better understand reasons for crop changes. Several cereals and pulses that were previously important subsistence crops are now grown as comparatively minor crops. The replacement of the
sagia
(waterwheel) by diesel pump irrigation, the introduction of commercial crops, and the reduction of the annual flood have led to fundamentally new cropping patterns within household farms. At the same time, each species has its own narrative and timing of change. Shifts in crops grown are paralleled by transitions in foodways, associated material culture, and land use. The project is timely, as much of the information about past crop uses resides in the memories of elderly farmers. The findings highlight the broader global need to document endangered memories of cropping patterns, traditional ecological and food knowledge, including local terms for foods and crops.
We have reconstructed long-term shifts in catchment sediment sources by analysing, for the first time, the strontium (Sr) and neodymium (Nd) isotope composition of dated floodplain deposits in the ...Desert Nile. The sediment load of the Nile has been dominated by material from the Ethiopian Highlands for much of the Holocene, but tributary wadis and aeolian sediments in Sudan and Egypt have also made major contributions to valley floor sedimentation. The importance of these sources has shifted dramatically in response to global climate changes. During the African Humid Period, before c. 4.5 ka, when stronger boreal summer insolation produced much higher rainfall across North Africa, the Nile floodplain in northern Sudan shows a tributary wadi input of 40–50%. Thousands of tributary wadis were active at this time along the full length of the Saharan Nile in Egypt and Sudan. As the climate became drier after 4.5 ka, the valley floor shows an abrupt fall in wadi inputs and a stronger Blue Nile/Atbara contribution. In the arid New Kingdom and later periods, in palaeochannel fills on the margins of the valley floor, aeolian sediments replace wadi inputs as the most important secondary contributor to floodplain sedimentation. Our sediment source data do not show a measurable contribution from the White Nile to the floodplain deposits of northern Sudan over the last 8500 years. This can be explained by the distinctive hydrology and sediment delivery dynamics of the upper Nile basin. High strontium isotope ratios observed in delta and offshore records – that were previously ascribed to a stronger White Nile input during the African Humid Period – may have to be at least partly reassessed. Our floodplain Sr records also have major implications for bioarchaeologists who carry out Sr isotope-based investigations of ancient human remains in the Nile Valley because the isotopic signature of Nile floodplain deposits has shifted significantly over time.
•The first strontium isotope record for the floodplains of the Holocene Nile.•Sheds new light on sediment source shifts in response to Holocene climate change and quantifies them for the first time.•Sheds new light on the sediment delivery dynamics of the entire Nile basin.•These records have important implications for the strontium-based studies of ancient populations in the Nile Valley.•Identifies the end of the African Humid Period in northern Sudan.
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