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Brainjacking: Implant Security Issues in Invasive Neuromodulation.
The security of medical devices is critical to good patient care, especially when the devices are implanted. In light of recent developments in information security, there is reason to be concerned that medical implants are vulnerable to attack. The ability of attackers to exert malicious control over brain implants ("brainjacking") has unique challenges that we address in this review, with particular focus on deep brain stimulation implants. To illustrate the potential severity of this risk, we identify several mechanisms through which attackers could manipulate patients if unauthorized access to an implant can be achieved. These include blind attacks in which the attacker requires no patient-specific knowledge and targeted attacks that require patient-specific information. Blind attacks include cessation of stimulation, draining implant batteries, inducing tissue damage, and information theft. Targeted attacks include impairment of motor function, alteration of impulse control, modification of emotions or affect, induction of pain, and modulation of the reward system. We also discuss the limitations inherent in designing implants and the trade-offs that must be made to balance device security with battery life and practicality. We conclude that researchers, clinicians, manufacturers, and regulatory bodies should cooperate to minimize the risk posed by brainjacking.
Pattern classification of deep brain local field potentials for brain computer interfaces
The trend of current brain computer interfaces (BCI) seek to establish bi-directional communication with the brain, for instance, recovering motor functions by externally controlling devices and directly stimulating the brain. This will greatly assist paralyzed individuals through bypassing the damaged brain region. The key process of this communication interface is to decode movements from neural signals and encode information into neural activity. The majority of decoding or pattern classification studies have focused on cortical areas for BCIs, but deep brain structures have also been involved in motor control. The subthalamic nucleus (STN) in the basal ganglia is involved in the preparation, execution and imagining of movements, and may be an alternative source for driving BCIs. This study therefore aimed to classify patterns of deep brain local field potentials (LFPs) related to execution of visually cued movements. LFPs were recorded bilaterally from the STN through deep brain stimulation electrodes implanted in patients with Parkinson's disease. The frequency dependent components of the LFPs were extracted using the wavelet packet transform. In each frequency component, signal features were extracted using an alternative approach called neural synchronization by analyzing Granger causality between the STN. Based on these extracted features, a new feature selection strategy, namely weighted sequential feature selection (WSFS) was developed to efficiently select the optimal feature subset. A support vector machine (SVM) classifier was implemented alongside this novel feature extraction and selection strategy, and evaluated using a cross-validation procedure. Using this optimised feature subset, average correct pattern classification accuracy of movement (left or right) reached 76.0±3.1%. The results obtained in this study are encouraging and suggest that the neural activity in the deep neural circuit (basal ganglia) can be used for controlling BCIs. © 2012 IEEE.
The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure.
Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.
Cerebellar Function in Developmental Dyslexia
Developmental dyslexia is a genetically based neurobiological syndrome, which is characterized by reading difficulty despite normal or high general intelligence. Even remediated dyslexic readers rarely achieve fast, fluent reading. Some dyslexics also have impairments in attention, short-term memory, sequencing (letters, word sounds, and motor acts), eye movements, poor balance, and general clumsiness. The presence of "cerebellar" motor and fluency symptoms led to the proposal that cerebellar dysfunction contributes to the etiology of dyslexia. Supporting this, functional imaging studies suggest that the cerebellum is part of the neural network supporting reading in typically developing readers, and reading difficulties have been reported in patients with cerebellar damage. Differences in both cerebellar asymmetry and gray matter volume are some of the most consistent structural brain findings in dyslexics compared with good readers. Furthermore, cerebellar functional activation patterns during reading and motor learning can differ in dyslexic readers. Behaviorally, some children and adults with dyslexia show poorer performance on cerebellar motor tasks, including eye movement control, postural stability, and implicit motor learning. However, many dyslexics do not have cerebellar signs, many cerebellar patients do not have reading problems, and differences in dyslexic brains are found throughout the whole reading network, and not isolated to the cerebellum. Therefore, impaired cerebellar function is probably not the primary cause of dyslexia, but rather a more fundamental neurodevelopmental abnormality leads to differences throughout the reading network. © 2012 Springer Science+Business Media, LLC.
Manifestations of developmental dyslexia in monolingual Persian speaking students.
BACKGROUND: Manifestations of dyslexia depend on language systems and scripts. This study explored the prevalence and clinical features of developmental dyslexia among monolingual Persian students and provided insights on mechanisms involved in reading Persian. METHODS: To measure reading ability we developed a new instrument, Analysis of Persian Reading Ability, which had acceptable validity and reliability. A total of 1562 children aged 6 ½ - 14 were randomly selected from a population of 109696 primary school students in the city of Qom, Iran. RESULTS: Using a variety of statistical and clinical criteria, 82 (5.2%) of the sample were classified as dyslexics. A detailed analysis of reading errors revealed eight types of errors related to three categories. The most frequent category in both dyslexic and the matched control group was phonological, followed by pragmatic and visual errors. CONCLUSION: The observed prevalence rate of dyslexia and reading error categories would suggest that Persian in vowel-free format is an opaque language and predominant use of a sub-lexical strategy is involved when reading Persian.
Identification of candidate genes for dyslexia susceptibility on chromosome 18.
BACKGROUND: Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis. METHODOLOGY/PRINCIPAL FINDINGS: Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R), dymeclin (DYM) and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L). CONCLUSIONS: Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.
Dynamic visual perception and reading development in Chinese school children.
The development of reading skills may depend to a certain extent on the development of basic visual perception. The magnocellular theory of developmental dyslexia assumes that deficits in the magnocellular pathway, indicated by less sensitivity in perceiving dynamic sensory stimuli, are responsible for a proportion of reading difficulties experienced by dyslexics. Using a task that measures coherent motion detection threshold, this study examined the relationship between dynamic visual perception and reading development in Chinese children. Experiment 1 compared the performance of 27 dyslexics and their age- and IQ-matched controls in the coherent motion detection task and in a static pattern perception task. Results showed that only in the former task did the dyslexics have a significantly higher threshold than the controls, suggesting that Chinese dyslexics, like some of their Western counterparts, may have deficits in magnocellular pathway. Experiment 2 examined whether dynamic visual processing affects specific cognitive processes in reading. One hundred fifth-grade children were tested on visual perception and reading-related tasks. Regression analyses found that the motion detection threshold accounted for 11% and 12%, respectively, variance in the speed of orthographic similarity judgment and in the accuracy of picture naming after IQ and vocabulary size were controlled. The static pattern detection threshold could not account for any variance. It is concluded that reading development in Chinese depends to a certain extent on the development of dynamic visual perception and its underlying neural pathway and that the impact of visual development can be specifically related to orthographic processing in reading Chinese.
Association of the KIAA0319 dyslexia susceptibility gene with reading skills in the general population.
OBJECTIVE: The authors previously identified a haplotype on chromosome 6p22 defined by three single-nucleotide polymorphisms (SNPs) that was associated with dyslexia (reading disability) in two independent samples of families that included at least one sibling with severe reading impairment. The authors also showed that this haplotype is associated with a reduction in expression of the KIAA0319 gene. In addition, a completely independent study detected an association between KIAA0319 markers and reading disability. In the current study, the authors tested whether the KIAA0319 gene influences reading skills in the general population, rather than having an effect restricted to reading disability. METHOD: The authors genotyped four SNPs that previously showed association with reading disability in the population of 7-9-year-old children in the Avon Longitudinal Study of Parents and Children (ALSPAC), a large longitudinal cohort for which reading-related phenotypes were available for more than 6,000 individuals. The authors conducted quantitative analysis for both single markers and haplotypes. RESULTS: The rs2143340 SNP, which effectively tags the three-SNP risk haplotype, was significantly associated with a test for reading ability. The risk haplotype itself also showed association with poor reading performance, and as in previous research, the association was stronger when the analysis was controlled for IQ. CONCLUSIONS: These results both support a role of the KIAA0319 gene in the development of dyslexia and suggest that this gene influences reading ability in the general population. Moreover, the data implicate the three-SNP haplotype and its tagging SNP rs2143340 as genetic risk factors for poor reading performance.
Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia.
The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to developmental dyslexia (DD). Two candidate genes within this region have recently been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have shown association with DD in a US and a German sample. However, when we genotyped these specific variants in two large, independent UK samples, we obtained only weak, inconsistent evidence for their involvement in DD. Having previously found evidence that variation in the KIAA0319 gene confers susceptibility to DD, we sought to refine this genetic association by genotyping 36 additional SNPs in the gene. Nine SNPs, predominantly clustered around the first exon, showed the most significant association with DD in one or both UK samples, including rs3212236 in the 5' flanking region (P = 0.00003) and rs761100 in intron 1 (P = 0.0004). We have thus refined the region of association with developmental dyslexia to putative regulatory sequences around the first exon of the KIAA0319 gene, supporting the presence of functional mutations that could affect gene expression. Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing.
A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States.
Several quantitative trait loci (QTLs) that influence developmental dyslexia (reading disability [RD]) have been mapped to chromosome regions by linkage analysis. The most consistently replicated area of linkage is on chromosome 6p23-21.3. We used association analysis in 223 siblings from the United Kingdom to identify an underlying QTL on 6p22.2. Our association study implicates a 77-kb region spanning the gene TTRAP and the first four exons of the neighboring uncharacterized gene KIAA0319. The region of association is also directly upstream of a third gene, THEM2. We found evidence of these associations in a second sample of siblings from the United Kingdom, as well as in an independent sample of twin-based sibships from Colorado. One main RD risk haplotype that has a frequency of approximately 12% was found in both the U.K. and U.S. samples. The haplotype is not distinguished by any protein-coding polymorphisms, and, therefore, the functional variation may relate to gene expression. The QTL influences a broad range of reading-related cognitive abilities but has no significant impact on general cognitive performance in these samples. In addition, the QTL effect may be largely limited to the severe range of reading disability.
A comparison of photoplethysmography and ECG recording to analyse heart rate variability in healthy subjects.
Measures of heart rate variability (HRV) are widely used to assess autonomic nervous system (ANS) function. The signal from which they are derived requires accurate determination of the interval between successive heartbeats; it can be recorded via electrocardiography (ECG), which is both non-invasive and widely available. However, methodological problems inherent in the recording and analysis of ECG traces have motivated a search for alternatives. Photoplethysmography (PPG) constitutes another means of determining the timing of cardiac cycles via continuous monitoring of changes in blood volume in a portion of the peripheral microvasculature. This technique measures pulse waveforms, which in some instances may prove a practical basis for HRV analysis. We investigated the feasibility of using earlobe PPG to analyse HRV by applying the same analytic process to PPG and ECG recordings made simultaneously. Comparison of 5-minute recordings demonstrated a very high degree of correlation in the temporal and frequency domains and in nonlinear dynamic analyses between HRV measures derived from PPG and ECG. Our results confirm that PPG provides accurate interpulse intervals from which HRV measures can be accurately derived in healthy subjects under ideal conditions, suggesting this technique may prove a practical alternative to ECG for HRV analysis. This finding is of particular relevance to the care of patients suffering from peripheral hyperkinesia or tremor, which make fingertip PPG recording impractical, and following clinical interventions known to introduce electrical artefacts into the electrocardiogram.