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Sunday, June 10, 2018

Research on meditation

From Wikipedia, the free encyclopedia
EEG technology has been used for meditation research

For the purpose of this article, research on meditation concerns research into the psychological and physiological effects of meditation using the scientific method. In recent years, these studies have increasingly involved the use of modern scientific techniques and instruments, such as fMRI and EEG which are able to directly observe brain physiology and neural activity in living subjects, either during the act of meditation itself, or before and after a meditation effort, thus allowing linkages to be established between meditative practice and changes in brain structure or function.

Since the 1950s hundreds of studies on meditation have been conducted. Yet, many of the early studies were flawed and thus yielded unreliable results.[1][2] Contemporary studies have attempted to address many of these flaws with the hope of guiding current research into a more fruitful path.[3] In 2013, researchers at Johns Hopkins, publishing in the Journal of the American Medical Association, identified 47 studies that qualify as well-designed and therefore reliable. Based on these studies, they concluded that there is moderate evidence that meditation reduces anxiety, depression, and pain, but there is no evidence that meditation is more effective than active treatment.[4] 2017 commentary was similarly mixed.[5][6]

The process of meditation, as well as its effects, is a growing subfield of neurological research.[7][8] Modern scientific techniques and instruments, such as fMRI and EEG, have been used to study how regular meditation affects individuals by measuring brain and bodily changes.[7][9][10]

Meditation is a broad term which encompasses a number of practices.[vague][citation needed]

Weaknesses in historic meditation and mindfulness research

A comparison of the effect of various meditation techniques on systolic blood pressure.[1]

In June, 2007 the United States National Center for Complementary and Integrative Health (NCCIH) published an independent, peer-reviewed, meta-analysis of the state of meditation research, conducted by researchers at the University of Alberta Evidence-based Practice Center. The report reviewed 813 studies involving five broad categories of meditation: mantra meditation, mindfulness meditation, yoga, T'ai chi, and Qigong, and included all studies on adults through September 2005, with a particular focus on research pertaining to hypertension, cardiovascular disease, and substance abuse. The report concluded, "Scientific research on meditation practices does not appear to have a common theoretical perspective and is characterized by poor methodological quality. Firm conclusions on the effects of meditation practices in healthcare cannot be drawn based on the available evidence. Future research on meditation practices must be more rigorous in the design and execution of studies and in the analysis and reporting of results." (p. 6) It noted that there is no theoretical explanation of health effects from meditation common to all meditation techniques.[1]

A version of this report subsequently published in the Journal of Alternative and Complementary Medicine stated that "Most clinical trials on meditation practices are generally characterized by poor methodological quality with significant threats to validity in every major quality domain assessed". This was the conclusion despite a statistically significant increase in quality of all reviewed meditation research, in general, over time between 1956 and 2005. Of the 400 clinical studies, 10% were found to be good quality. A call was made for rigorous study of meditation.[3] These authors also noted that this finding is not unique to the area of meditation research and that the quality of reporting is a frequent problem in other areas of complementary and alternative medicine (CAM) research and related therapy research domains.

Of more than 3,000 scientific studies that were found in a comprehensive search of 17 relevant databases, only about 4% had randomised controlled trials (RCTs), which are designed to exclude the placebo effect.[1]

A 2013 statement from the American Heart Association evaluated the evidence for the effectiveness of TM as a treatment for hypertension as "unknown/unclear/uncertain or not well-established", and stated: "Because of many negative studies or mixed results and a paucity of available trials... other meditation techniques are not recommended in clinical practice to lower BP at this time."[11]

2017 commentary was similarly mixed,[5][6] with concerns including the particular characteristics of individuals who tend to participate in mindfulness and meditation research.[12]

Mindfulness

One meta-analysis supported the use of Mindfulness-Based Stress Reduction (MBSR) to alleviate symptoms of a variety of mental and physical disorders.[13] A previous study commissioned by the US Agency for Healthcare Research and Quality found that meditation interventions reduce multiple negative dimensions of psychological stress.[4] Other systematic reviews and meta-analysis show that mindfulness meditation has several mental health benefits such as bringing about reductions in depression symptoms,[14][15][16] and mindfulness interventions also appear to be a promising intervention for managing depression in youth.[17][18] Mindfulness meditation is useful for managing stress,[15][19][20] anxiety,[14][15][20] and also appears to be effective in treating substance use disorders.[21][22][23] A recent meta analysis by Hilton et al. (2016) including 30 randomized controlled trials found high quality evidence for improvement in depressive symptoms.[24] Other review studies have shown that mindfulness meditation can enhance the psychological functioning of breast cancer survivors,[15] effective for eating disorders,[25][26] and may also be effective in treating psychosis.[27][28][29]
Studies have also shown that rumination and worry contribute to mental illnesses such as depression and anxiety,[30] and mindfulness-based interventions are effective in the reduction of worry.[30][31]

Some studies suggest that mindfulness meditation contributes to a more coherent and healthy sense of self and identity, when considering aspects such as sense of responsibility, authenticity, compassion, self-acceptance and character.[32][33]

Mindfulness scales

In the relatively new field of western psychological mindfulness, researchers attempt to define and measure the results of mindfulness primarily through controlled, randomised studies of mindfulness intervention on various dependent variables. The participants in mindfulness interventions measure many of the outcomes of such interventions subjectively. For this reason, several mindfulness inventories or scales (a set of questions posed to a subject whose answers output the subject's aggregate answers in the form of a rating or category) have arisen. Twelve such methods are mentioned by the Mindfulness Research Guide[34]

Brain mechanisms

In 2011, National Center for Complementary and Integrative Health (NCCIH) released findings from a study in which magnetic resonance images were taken of the brains of 16 participants 2 weeks before and after the participants joined the mindfulness meditation (MM) program by researchers from Massachusetts General Hospital, Bender Institute of Neuroimaging in Germany, and the University of Massachusetts Medical School. Researchers concluded that
..these findings may represent an underlying brain mechanism associated with mindfulness-based improvements in mental health.[35]
The analgesic effect of MM involves multiple brain mechanisms including the activation of the anterior cingulate cortex and the ventromedial prefrontal cortex.[36] In addition, brief periods of MM training increases the amount of grey matter in the hippocampus and parietal lobe.[37] Other neural changes resulting from MM may increase the efficiency of attentional control.[38]

Participation in MBSR programmes has been found to correlate with decreases in right basolateral amygdala gray matter density,[39] and increases in gray matter concentration within the left hippocampus.[40]

Changes in the brain

Mindfulness meditation also appears to bring about favorable structural changes in the brain, though more research needs to be done because most of these studies are small and have weak methodology.[41][7][9][10] One recent study found a significant cortical thickness increase in individuals who underwent a brief -8 weeks- MBSR training program and that this increase was coupled with a significant reduction of several psychological indices related to worry, state anxiety, depression.[42] Another study describes how mindfulness based interventions target neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface.[22] A meta-analysis by Fox et al. (2014) using results from 21 brain imaging studies found consistent differences in the region of the prefrontal cortex and other brain regions associated with body awareness. In terms of effect size the mean effect was rated as moderate. (Cohen's d = 0.46) However the results should be interpreted with caution because funnel plots indicate that publication bias is an issue in meditation research.[41] A follow up by Fox et al. (2016) using 78 functional neuro-imaging studies suggests that different meditation styles are reliably associated with different brain activity. Activations in some brain regions are usually accompanied by deactivation in others. This finding suggests that meditation research must put emphasis on comparing practices from the same style of meditation, for example results from studies investigating focused attention methods cannot be compared to results from open monitoring approaches.[43]

Attention and mindfulness

Attention networks and mindfulness meditation

Psychological and Buddhist conceptualisations of mindfulness both highlight awareness and attention training as key components, in which levels of mindfulness can be cultivated with practise of mindfulness meditation.[44] Focused attention meditation and open monitoring meditation are distinct types of mindfulness meditation, and the former relates to directing and maintaining attention on a chosen object (e.g. the breath).[45] Open monitoring meditation does not involve focus on a specific object, and instead awareness is grounded in the perceptual features of one’s environment.

Focused attention meditation is typically practiced first to increase the ability to enhance attentional stability, and awareness of mental states with the goal being to transition to open monitoring meditation practise that emphasizes the ability to monitor moment-by-moment changes in experience, without a focus of attention to maintain. Mindfulness meditation may lead to greater cognitive flexibility [46]

Evidence for improvements in three areas of attention

Sustained attention Tasks of sustained attention relate to vigilance and the preparedness that aids completing a particular task goal. Psychological research into the relationship between mindfulness meditation and the sustained attention network have revealed the following:
  • Mindfulness meditators have demonstrated superior performance when the stimulus to be detected in a task was unexpected, relative to when it was expected. This suggests that attention resources were more readily available in order to perform well in the task. This was despite not receiving a visual cue to aid performance. (Valentine & Sweet, 1999).
  • In a Continuous performance task [47] an association was found between higher dispositional mindfulness and more stable maintenance of sustained attention.
  • In an EEG study,[48] the Attentional blink effect was reduced, and P3b ERP amplitude decreased in a group of participants that completed a mindfulness retreat.[49] The incidence of reduced attentional blink effect relates to an increase in detectability of a second target. This may have been due to a greater ability to allocate attentional resources for detecting the second target, reflected in a reduced P3b amplitude.
  • A greater degree of attentional resources may also be reflected in faster response times in task performance, as was found for participants with higher levels of mindfulness experience.[50]
Selective attention
  • Selective attention as linked with the orientation network, is involved in selecting the relevant stimuli to attend to.
  • Performance in the ability to limit attention to potentially sensory inputs (i.e. selective attention) was found to be higher following the completion of an 8-week MBSR course, compared to a one-month retreat and control group (with no mindfulness training).[50] The ANT task is a general applicable task designed to test the three attention networks, in which participants are required to determine the direction of a central arrow on a computer screen.[51] Efficiency in orienting that represent the capacity to selectively attend to stimuli was calculated by examining changes in the reaction time that accompanied cues indicating where the target would occur relative to the aid of no cues.
  • Meditation experience was found to correlate negatively with reaction times on an Eriksen flanker task measuring responses to global and local figures. Similar findings have been observed for correlations between mindfulness experience in an orienting score of response times taken from Attention Network Task performance.[52]
Executive control attention Executive control attention include functions of inhibiting the conscious processing of distracting information. In the context of mindful meditation, distracting information would relate to attention grabbing mental events such as thoughts related to the future or past.[45]
  • More than one study have reported findings of a reduced Stroop effect following mindfulness meditation training.[46][53][54] The Stroop effect indexes interference created by having words printed in colour that differ to the read semantic meaning e.g. green printed in red. However findings for this task are not consistently found.[55][10] For instance the MBSR may differ to how mindful one becomes relative to a person who is already high in trait mindfulness.[38]
  • Using the Attention Network Task (a version of Eriksen flanker task [51]) it was found that error scores that indicate executive control performance were reduced in experienced meditators [50] and following a brief 5 session mindfulness training program.[53]
  • A neuroimaging study supports behavioural research findings that higher levels of mindfulness are associated with greater proficiency to inhibit distracting information. As greater activation of the rostral anterior cingulate cortex (ACC) was shown for mindfulness meditators than matched controls.
  • Following a Stroop test, reduced amplitude of the P3 ERP component was found for a meditation group relative to control participants. This was taken to signify that mindfulness meditation improves executive control functions of attention. An increased amplitude in the N2 ERP component was also observed in the mindfulness meditation group, thought to reflect more efficient perceptual discrimination in earlier stages of perceptual processing.[56]

Emotion regulation and mindfulness

Reductions in rumination have been found following Mindfulness meditation practise.[57][58]

Evidence of mindfulness and emotion regulation outcomes

Emotional reactivity can be measured and reflected in brain regions related to the production of emotions.[59] It can also be reflected in tests of attentional performance, indexed in poorer performance in attention related tasks. The regulation of emotional reactivity as initiated by attentional control capacities can be taxing to performance, as attentional resources are limited [60]
  • Patients with social anxiety disorder (SAD) exhibited reduced amygdala activation in response to negative self-beliefs following an MBSR intervention program that involves mindfulness meditation practise [61]
  • The LPP ERP component indexes arousal and is larger in amplitude for emotionally salient stimuli relative to neutral.[62][63][64] Individuals higher in trait mindfulness showed lower LPP responses to high arousal unpleasant images. These findings suggest that individuals with higher trait mindfulness were better able to regulate emotional reactivity to emotionally evocative stimuli.[65]
  • Participants that completed a 7-week mindfulness training program demonstrated a reduction in a measure of emotional interference (measured as slower responses times following the presentation of emotional relative to neutral pictures). This suggests a reduction in emotional interference.[66]
  • Following a MBSR intervention, decreases in social anxiety symptom severity were found, as well as increases in bilateral parietal cortex neural correlates. This is thought to reflect the increased employment of inhibitory attentional control capacities to regulate emotions [67][68]
  • Mindfulness has been found to reduce subsequent distress.[69]

Controversies in mindful emotion regulation

It is debated as to whether top-down executive control regions such as the Dorsolateral prefrontal cortex (DLPFC),[70] are required [68] or not [61] to inhibit reactivity of the amygdala activation related to the production of evoked emotional responses. Arguably an initial increase in activation of executive control regions developed during mindfulness training may lessen with increasing mindfulness expertise [71]

Prevention of mental illness

An 8 week mindfulness course given to students was found to reduce the number subsequently needing treatment for mental illness by 60%, although the study was not of large size and commented that the effect could be due to 'non-specific effects', as the control group had received no attention at all, rather than an alternative intervention.[69]

Future directions

A large part of mindfulness research is dependent on technology. As new technology continues to be developed, new imaging techniques will become useful in this field. It would be interesting to use real-time fMRI to help give immediate feedback and guide participants through the programs. It could also be used to more easily train and evaluate mental states during meditation itself.[72] The new technology in the upcoming years offers many exciting potentials for the continued research.

Research on other types of meditation

Cortical Areas Thicker in Meditators .jpg

Insight (Vipassana) meditation

Vipassana meditation is a component of Buddhist philosophy. Phra Taweepong Inwongsakul and Sampath Kumar from the University of Mysore have been studying the effects of this meditation on 120 students by measuring the associated increase of cortical thickness in the brain. The results of this study are inconclusive.[73][74]

Sahaja yoga and mental silence

Sahaja yoga meditation is regarded as a mental silence meditation, and has been shown to correlate with particular brain[75][76] and brain wave[77][78][79] characteristics. One study has led to suggestions that Sahaja meditation involves 'switching off' irrelevant brain networks for the maintenance of focused internalized attention and inhibition of inappropriate information.[80] Sahaja meditators appear to benefit from lower depression[81] and scored above control group for emotional well-being and mental health measures on SF-36 ratings.[82][83][84]

A study comparing practitioners of Sahaja Yoga meditation with a group of non meditators doing a simple relaxation exercise, measured a drop in skin temperature in the meditators compared to a rise in skin temperature in the non meditators as they relaxed. The researchers noted that all other meditation studies that have observed skin temperature have recorded increases and none have recorded a decrease in skin temperature. This suggests that Sahaja Yoga meditation, being a mental silence approach, may differ both experientially and physiologically from simple relaxation.[79]

Kundalini Yoga

Kundalini Yoga has proved to increase the prevention of cognitive decline and evaluate the response of biomarkers to treatment, thereby shedding light on the underlying mechanisms of the link between Kundalini Yoga and cognitive impairment. For the study, 81 participants aged 55 and older who had subjective memory complaints and met criteria for mild cognitive impairment, indicated by a total score of 0.5 on the Clinical Dementia Rating Scale. The results showed that at 12 weeks, both the yoga group showed significant improvements in recall memory and visual memory and showed significant sustained improvement in memory up to the 24-week follow-up, the yoga group showed significant improvement in verbal fluency and sustained significant improvements in executive functioning at week 24. In addition, the yoga cohort showed significant improvement in depressive symptoms, apathy, and resilience from emotional stress. This research was provided by Helen Lavretsky, M.D. and colleagues.[85] In another study, Kundalini Yoga did not show significant effectiveness in treating obsessive-compulsive disorders compared with Relaxation/Meditation.[86]

Transcendental Meditation

The first Transcendental Meditation (TM) research studies were conducted at UCLA and Harvard University and published in Science and the American Journal of Physiology in 1970 and 1971.[87] However, much research has been of poor quality,[1][86][88] including a high risk for bias due to the connection of researchers to the TM organization and the selection of subjects with a favorable opinion of TM.[89][90][91] Independent systematic reviews have not found health benefits for TM exceeding those of relaxation and health education.[1][86][90] A 2013 statement from the American Heart Association described the evidence supporting TM as a treatment for hypertension as Level IIB, meaning that TM "may be considered in clinical practice" but that its effectiveness is "unknown/unclear/uncertain or not well-established".[this quote needs a citation] In another study, TM proved comparable with other kinds of relaxation therapies in reducing anxiety.[86]

Research on unspecified or multiple types of meditation

Brain activity

The medial prefrontal and posterior cingulate cortices have been found to be relatively deactivated during meditation (experienced meditators using concentration, lovingkindness and choiceless awareness meditation). In addition experienced meditators were found to have stronger coupling between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices both when meditating and when not meditating.[92]

Mental health

A meta analysis found meditation gave some benefits, but no evidence that it was better than other treatments, for mental illness.[4]

Physical changes in the brain

Meditation has been shown to change grey matter concentrations and the precuneus.[93][40][94][41][39]

An eight-week MBSR course induced changes in gray matter concentrations.[40] Exploratory whole brain analyses identified significant increases in gray matter concentration in the PCC, TPJ, and the cerebellum. These results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes, emotion regulation, self-referential processing, and perspective taking.

Perception

Studies have shown that meditation has both short-term and long-term effects on various perceptual faculties. In 1984 a study showed that meditators have a significantly lower detection threshold for light stimuli of short duration.[95] In 2000 a study of the perception of visual illusions by zen masters, novice meditators, and non-meditators showed statistically significant effects found for the Poggendorff Illusion but not for the Müller-Lyer Illusion. The zen masters experienced a statistically significant reduction in initial illusion (measured as error in millimeters) and a lower decrement in illusion for subsequent trials.[96] Tloczynski has described the theory of mechanism behind the changes in perception that accompany mindfulness meditation thus: "A person who meditates consequently perceives objects more as directly experienced stimuli and less as concepts… With the removal or minimization of cognitive stimuli and generally increasing awareness, meditation can therefore influence both the quality (accuracy) and quantity (detection) of perception."[96] Brown also points to this as a possible explanation of the phenomenon: "[the higher rate of detection of single light flashes] involves quieting some of the higher mental processes which normally obstruct the perception of subtle events."[this quote needs a citation] In other words, the practice may temporarily or permanently alter some of the top-down processing involved in filtering subtle events usually deemed noise by the perceptual filters.[citation needed]

Relaxation response

Herbert Benson, founder of the Mind-Body Medical Institute, which is affiliated with Harvard University and several Boston hospitals, reports that meditation induces a host of biochemical and physical changes in the body collectively referred to as the "relaxation response".[97] The relaxation response includes changes in metabolism, heart rate, respiration, blood pressure and brain chemistry. Benson and his team have also done clinical studies at Buddhist monasteries in the Himalayan Mountains.[98] Benson wrote The Relaxation Response to document the benefits of meditation, which in 1975 were not yet widely known.[99]

Calming effects

According to an article in Psychological Bulletin, EEG activity slows as a result of meditation.[100] The National Institutes of Health (NIH) has written, "It is thought that some types of meditation might work by reducing activity in the sympathetic nervous system and increasing activity in the parasympathetic nervous system,"[this quote needs a citation] or equivalently, that meditation produces a reduction in arousal and increase in relaxation.[citation needed]

Slowing aging

Aging is a process accompanied by a decrease in brain weight and volume. This phenomenon can be explained by structural changes in the brain, namely, a loss of grey matter. Some studies over the last decade have implicated meditation as a protective factor against normal age-related brain atrophy.[101] The first direct evidence for this link emerged from a study investigating changes in the cortical thickness of meditators. Interestingly, the researchers found that regular meditation practice was able to reduce age-related thinning of the frontal cortex, albeit, these findings were restricted to particular regions of the brain.[102] A similar study looked to further expand on this finding by including a behavioural component. Consistent with the previous study, meditators did not show the expected negative correlation between grey matter volume and age. In addition, the results for meditators on the behavioural test, measuring attentional performance, were comparable across all age groups.[103] This implies that meditation can potentially protect against age-related grey matter loss and age-related cognitive decline. Since then, more research has supported the notion that meditation serves as a neuroprotective factor that slows age-related brain atrophy.[101][104] Still, all studies have been cross sectional in design. Furthermore, these results merely describe associations and do not make causal inferences.[105] Further work using longitudinal and experimental designs may help solidify the causal link between meditation and grey matter loss. Since few studies have investigated this direct link, however insightful they may be, there is not sufficient evidence for a conclusive answer.

Research has also been conducted on the malleable determinants of cellular aging in an effort to understand human longevity. Researchers have stated, "We have reviewed data linking stress arousal and oxidative stress to telomere shortness. Meditative practices appear to improve the endocrine balance toward positive arousal (high DHEA, lower cortisol) and decrease oxidative stress. Thus, meditation practices may promote mitotic cell longevity both through decreasing stress hormones and oxidative stress and increasing hormones that may protect the telomere."[106][107]

Happiness

Studies have shown meditators to have higher happiness than control groups, although this may be due to non-specific factors such as meditators having better general self-care.[108][109][82][110]
Yongey Mingyur Rinpoche has said that neuro scientists have found that with meditation, an individual's happiness baseline can change.[111]

Positive relationships have been found between the volume of gray matter in the right precuneus area of the brain and both meditation and the subject's subjective happiness score.[112][93][40][94][41][39]

Potential adverse effects and limits of meditation

The following is an official statement from the US government-run National Center for Complementary and Integrative Health:
"Meditation is considered to be safe for healthy people. There have been rare reports that meditation could cause or worsen symptoms in people who have certain psychiatric problems, but this question has not been fully researched. People with physical limitations may not be able to participate in certain meditative practices involving physical movement. Individuals with existing mental or physical health conditions should speak with their health care providers prior to starting a meditative practice and make their meditation instructor aware of their condition."[113]
Adverse effects have been reported,[114][115] and may, in some cases, be the result of "improper use of meditation".[116] The NIH advises prospective meditators to "ask about the training and experience of the meditation instructor… [they] are considering."[113]

As with any practice, meditation may also be used to avoid facing ongoing problems or emerging crises in the meditator's life. In such situations, it may instead be helpful to apply mindful attitudes acquired in meditation while actively engaging with current problems.[117][118] According to the NIH, meditation should not be used as a replacement for conventional health care or as a reason to postpone seeing a doctor.[113]

Pain

Meditation reduces pain perception.[119]

Neuroplasticity

From Wikipedia, the free encyclopedia

Neuroplasticity, also known as brain plasticity and neural plasticity, is the ability of the brain to change throughout an individual's life, e.g., brain activity associated with a given function can be transferred to a different location, the proportion of grey matter can change, and synapses may strengthen or weaken over time.

Research in the latter half of the 20th century showed that many aspects of the brain can be altered (or are "plastic") even through adulthood.[1][2][3][4] This notion is in contrast with the previous scientific consensus that the brain develops during a critical period in early childhood and then remains relatively unchanged (or "static").[5]

Neuroplasticity can be observed at multiple scales, from microscopic changes in individual neurons to larger-scale changes such as cortical remapping in response to injury.[6] Behavior, environmental stimuli, thought, and emotions may also cause neuroplastic change through activity-dependent plasticity, which has significant implications for healthy development, learning, memory, and recovery from brain damage.[6][7][8]

At the single cell level, synaptic plasticity refers to changes in the connections between neurons, whereas non-synaptic plasticity refers to changes in their intrinsic excitability.

Neurobiology

One of the fundamental principles underlying neuroplasticity is based on the idea that individual synaptic connections are constantly being removed or recreated, largely dependent upon the activity of the neurons that bear them. The activity-dependence of synaptic plasticity is captured in the aphorism which is often used to summarize Hebbian theory: "neurons that fire together, wire together"/"neurons that fire out of sync, fail to link". If two nearby neurons often produce an impulse in close temporal proximity, their functional properties may converge. Conversely, neurons that are not regularly activated simultaneously may be less likely to functionally converge.

Cortical maps

Cortical organization, especially in sensory systems, is often described in terms of maps.[9] For example, sensory information from the foot projects to one cortical site and the projections from the hand target another site. As a result, the cortical representation of sensory inputs from the body resembles a somatotopic map, often described as the sensory homunculus.

In the late 1970s and early 1980s, several groups began exploring the impact of interfering with sensory inputs on cortical map reorganization. Michael Merzenich, Jon Kaas and Doug Rasmusson were some of those researchers. They found that if the cortical map is deprived of its input, it activates at a later time in response to other, usually adjacent inputs. Their findings have been since corroborated and extended by many research groups. Merzenich's (1984) study involved the mapping of owl monkey hands before and after amputation of the third digit. Before amputation, there were five distinct areas, one corresponding to each digit of the experimental hand. Sixty-two days following amputation of the third digit, the area in the cortical map formerly occupied by that digit had been invaded by the previously adjacent second and fourth digit zones. The areas representing digit one and five are not located directly beside the area representing digit three, so these regions remained, for the most part, unchanged following amputation.[10] This study demonstrates that only those regions that border a certain area invade it to alter the cortical map. In the somatic sensory system, in which this phenomenon has been most thoroughly investigated, JT Wall and J Xu have traced the mechanisms underlying this plasticity. Re-organization is not cortically emergent, but occurs at every level in the processing hierarchy; this produces the map changes observed in the cerebral cortex.[11]

Merzenich and William Jenkins (1990) initiated studies relating sensory experience, without pathological perturbation, to cortically observed plasticity in the primate somatosensory system, with the finding that sensory sites activated in an attended operant behavior increase in their cortical representation. Shortly thereafter, Ford Ebner and colleagues (1994) made similar efforts in the rodent whisker barrel cortex (also part of the somatosensory system). These two groups largely diverged over the years. The rodent whisker barrel efforts became a focus for Ebner, Matthew Diamond, Michael Armstrong-James, Robert Sachdev, and Kevin Fox. Great inroads were made in identifying the locus of change as being at cortical synapses expressing NMDA receptors, and in implicating cholinergic inputs as necessary for normal expression. The work of Ron Frostig and Daniel Polley (1999, 2004) identified behavioral manipulations causing a substantial impact on the cortical plasticity in that system.

Merzenich and DT Blake (2002, 2005, 2006) went on to use cortical implants to study the evolution of plasticity in both the somatosensory and auditory systems. Both systems show similar changes with respect to behavior. When a stimulus is cognitively associated with reinforcement, its cortical representation is strengthened and enlarged. In some cases, cortical representations can increase two to threefold in 1–2 days when a new sensory motor behavior is first acquired, and changes are largely finalised within at most a few weeks. Control studies show that these changes are not caused by sensory experience alone: they require learning about the sensory experience, they are strongest for the stimuli that are associated with reward, and they occur with equal ease in operant and classical conditioning behaviors.

An interesting phenomenon involving plasticity of cortical maps is the phenomenon of phantom limb sensation. Phantom limb sensation is experienced by people who have undergone amputations in hands, arms, and legs, but it is not limited to extremities. Although the neurological basis of phantom limb sensation is still not entirely understood it is believed that cortical reorganization plays an important role.[12]

Norman Doidge, following the lead of Michael Merzenich, separates manifestations of neuroplasticity into adaptations that have positive or negative behavioral consequences. For example, if an organism can recover after a stroke to normal levels of performance, that adaptiveness could be considered an example of "positive plasticity". Changes such as an excessive level of neuronal growth leading to spasticity or tonic paralysis, or excessive neurotransmitter release in response to injury that could result in nerve cell death, are considered as an example of "negative" plasticity. In addition, drug addiction and obsessive-compulsive disorder are both deemed examples of "negative plasticity" by Dr. Doidge, as the synaptic rewiring resulting in these behaviors is also highly maladaptive.[12][13]

A 2005 study found that the effects of neuroplasticity occur even more rapidly than previously expected. Medical students' brains were imaged during the period of studying for their exams. In a matter of months, the students' gray matter increased significantly in the posterior and lateral parietal cortex.[14]

Applications and example

The adult brain is not entirely "hard-wired" with fixed neuronal circuits. There are many instances of cortical and subcortical rewiring of neuronal circuits in response to training as well as in response to injury. There is solid evidence that neurogenesis (birth of brain cells) occurs in the adult, mammalian brain—and such changes can persist well into old age.[3] The evidence for neurogenesis is mainly restricted to the hippocampus and olfactory bulb, but current research has revealed that other parts of the brain, including the cerebellum, may be involved as well.[15]

There is now ample evidence[citation needed] for the active, experience-dependent re-organization of the synaptic networks of the brain involving multiple inter-related structures including the cerebral cortex. The specific details of how this process occurs at the molecular and ultrastructural levels are topics of active neuroscience research. The way experience can influence the synaptic organization of the brain is also the basis for a number of theories of brain function including the general theory of mind and Neural Darwinism. The concept of neuroplasticity is also central to theories of memory and learning that are associated with experience-driven alteration of synaptic structure and function in studies of classical conditioning in invertebrate animal models such as Aplysia.

Treatment of brain damage

A surprising consequence of neuroplasticity is that the brain activity associated with a given function can be transferred to a different location; this can result from normal experience and also occurs in the process of recovery from brain injury. Neuroplasticity is the fundamental issue that supports the scientific basis for treatment of acquired brain injury with goal-directed experiential therapeutic programs in the context of rehabilitation approaches to the functional consequences of the injury.

Neuroplasticity is gaining popularity as a theory that, at least in part, explains improvements in functional outcomes with physical therapy post-stroke. Rehabilitation techniques that are supported by evidence which suggest cortical reorganization as the mechanism of change include constraint-induced movement therapy, functional electrical stimulation, treadmill training with body-weight support, and virtual reality therapy. Robot assisted therapy is an emerging technique, which is also hypothesized to work by way of neuroplasticity, though there is currently insufficient evidence to determine the exact mechanisms of change when using this method.[16]

One group has developed a treatment that includes increased levels of progesterone injections in brain-injured patients. "Administration of progesterone after traumatic brain injury[17] (TBI) and stroke reduces edema, inflammation, and neuronal cell death, and enhances spatial reference memory and sensory motor recovery."[18] In a clinical trial, a group of severely injured patients had a 60% reduction in mortality after three days of progesterone injections.[19] However, a study published in the New England Journal of Medicine in 2014 detailing the results of a multi-center NIH-funded phase III clinical trial of 882 patients found that treatment of acute traumatic brain injury with the hormone progesterone provides no significant benefit to patients when compared with placebo.[20]

Vision

For decades, researchers assumed that humans had to acquire binocular vision, in particular stereopsis, in early childhood or they would never gain it. In recent years, however, successful improvements in persons with amblyopia, convergence insufficiency or other stereo vision anomalies have become prime examples of neuroplasticity; binocular vision improvements and stereopsis recovery are now active areas of scientific and clinical research.[21][22][23]

Brain training

Several companies have offered so-called cognitive training software programs for various purposes that claim to work via neuroplasticity; one example is Fast ForWord which is marketed to help children with learning disabilities.[24] A systematic meta-analytic review found that "There is no evidence from the analysis carried out that Fast ForWord is effective as a treatment for children's oral language or reading difficulties".[24] A 2016 review found very little evidence supporting any of the claims of Fast ForWord and other commercial products, as their task-specific effects fail to generalise to other tasks.[25]

Sensory prostheses

Neuroplasticity is involved in the development of sensory function. The brain is born immature and it adapts to sensory inputs after birth. In the auditory system, congenital hearing impairment, a rather frequent inborn condition affecting 1 of 1000 newborns, has been shown to affect auditory development, and implantation of a sensory prostheses activating the auditory system has prevented the deficits and induced functional maturation of the auditory system.[26] Due to a sensitive period for plasticity, there is also a sensitive period for such intervention within the first 2–4 years of life. Consequently, in prelingually deaf children, early cochlear implantation, as a rule, allows the children to learn the mother language and acquire acoustic communication.[27]

Phantom limbs

A diagrammatic explanation of the mirror box. The patient places the intact limb into one side of the box (in this case the right hand) and the amputated limb into the other side. Due to the mirror, the patient sees a reflection of the intact hand where the missing limb would be (indicated in lower contrast). The patient thus receives artificial visual feedback that the "resurrected" limb is now moving when they move the good hand.

In the phenomenon of phantom limb sensation, a person continues to feel pain or sensation within a part of their body that has been amputated. This is strangely common, occurring in 60–80% of amputees.[28] An explanation for this is based on the concept of neuroplasticity, as the cortical maps of the removed limbs are believed to have become engaged with the area around them in the postcentral gyrus. This results in activity within the surrounding area of the cortex being misinterpreted by the area of the cortex formerly responsible for the amputated limb.

The relationship between phantom limb sensation and neuroplasticity is a complex one. In the early 1990s V.S. Ramachandran theorized that phantom limbs were the result of cortical remapping. However, in 1995 Herta Flor and her colleagues demonstrated that cortical remapping occurs only in patients who have phantom pain.[29] Her research showed that phantom limb pain (rather than referred sensations) was the perceptual correlate of cortical reorganization.[30] This phenomenon is sometimes referred to as maladaptive plasticity.

In 2009 Lorimer Moseley and Peter Brugger carried out a remarkable experiment in which they encouraged arm amputee subjects to use visual imagery to contort their phantom limbs into impossible configurations. Four of the seven subjects succeeded in performing impossible movements of the phantom limb. This experiment suggests that the subjects had modified the neural representation of their phantom limbs and generated the motor commands needed to execute impossible movements in the absence of feedback from the body.[31] The authors stated that: "In fact, this finding extends our understanding of the brain's plasticity because it is evidence that profound changes in the mental representation of the body can be induced purely by internal brain mechanisms—the brain truly does change itself."

Chronic pain

Individuals who suffer from chronic pain experience prolonged pain at sites that may have been previously injured, yet are otherwise currently healthy. This phenomenon is related to neuroplasticity due to a maladaptive reorganization of the nervous system, both peripherally and centrally. During the period of tissue damage, noxious stimuli and inflammation cause an elevation of nociceptive input from the periphery to the central nervous system. Prolonged nociception from the periphery then elicits a neuroplastic response at the cortical level to change its somatotopic organization for the painful site, inducing central sensitization.[32] For instance, individuals experiencing complex regional pain syndrome demonstrate a diminished cortical somatotopic representation of the hand contralaterally as well as a decreased spacing between the hand and the mouth.[33] Additionally, chronic pain has been reported to significantly reduce the volume of grey matter in the brain globally, and more specifically at the prefrontal cortex and right thalamus.[34] However, following treatment, these abnormalities in cortical reorganization and grey matter volume are resolved, as well as their symptoms. Similar results have been reported for phantom limb pain,[35] chronic low back pain[36] and carpal tunnel syndrome.[37]

Meditation

A number of studies have linked meditation practice to differences in cortical thickness or density of gray matter.[4][38][39][40] One of the most well-known studies to demonstrate this was led by Sara Lazar, from Harvard University, in 2000.[41] Richard Davidson, a neuroscientist at the University of Wisconsin, has led experiments in cooperation with the Dalai Lama on effects of meditation on the brain. His results suggest that long-term or short-term practice of meditation results in different levels of activity in brain regions associated with such qualities as attention, anxiety, depression, fear, anger, and the ability of the body to heal itself. These functional changes may be caused by changes in the physical structure of the brain.[42][43][44][45]

Fitness and exercise

Aerobic exercise promotes adult neurogenesis by increasing the production of neurotrophic factors (compounds that promote growth or survival of neurons), such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF).[46][47][48] Exercise-induced neurogenesis in the hippocampus is associated with measurable improvements in spatial memory.[49][50][51][52] Consistent aerobic exercise over a period of several months induces marked clinically significant improvements in executive function (i.e., the "cognitive control" of behavior) and increased gray matter volume in multiple brain regions, particularly those that give rise to cognitive control.[48][49][53][54] The brain structures that show the greatest improvements in gray matter volume in response to aerobic exercise are the prefrontal cortex and hippocampus;[48][49][50] moderate improvements are seen in the anterior cingulate cortex, parietal cortex, cerebellum, caudate nucleus, and nucleus accumbens.[48][49][50] Higher physical fitness scores (measured by VO2 max) are associated with better executive function, faster processing speed, and greater volume of the hippocampus, caudate nucleus, and nucleus accumbens.[49]

Human echolocation

Human echolocation is a learned ability for humans to sense their environment from echoes. This ability is used by some blind people to navigate their environment and sense their surroundings in detail. Studies in 2010[55] and 2011[56] using functional magnetic resonance imaging techniques have shown that parts of the brain associated with visual processing are adapted for the new skill of echolocation. Studies with blind patients, for example, suggest that the click-echoes heard by these patients were processed by brain regions devoted to vision rather than audition.[57]

ADHD stimulants

Reviews of MRI studies on individuals with ADHD suggest that the long-term treatment of attention deficit hyperactivity disorder (ADHD) with stimulants, such as amphetamine or methylphenidate, decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.[58][59][60]

In children

Neuroplasticity is most active in childhood as a part of normal human development, and can also be seen as an especially important mechanism for children in terms of risk and resiliency.[61] Trauma is considered a great risk as it negatively affects many areas of the brain and puts strain on the sympathetic nervous system from constant activation. Trauma thus alters the brain’s connections such that children who have experienced trauma may be hyper vigilant or overly aroused.[62] However a child’s brain can cope with these adverse effects through the actions of neuroplasticity.[63]

In animals

In a single lifespan, individuals of an animal species may encounter various changes in brain morphology. Many of these differences are caused by the release of hormones in the brain; others are the product of evolutionary factors or developmental stages.[64][65][66][67] Some changes occur seasonally in species to enhance or generate response behaviors.

Seasonal brain changes

Changing brain behavior and morphology to suit other seasonal behaviors is relatively common in animals.[68] These changes can improve the chances of mating during breeding season.[64][65][66][68][69][70] Examples of seasonal brain morphology change can be found within many classes and species.

Within the class Aves, black-capped chickadees experience an increase in the volume of their hippocampus and strength of neural connections to the hippocampus during fall months.[71][72] These morphological changes within the hippocampus which are related to spatial memory are not limited to birds, as they can also be observed in rodents and amphibians.[68] In songbirds, many song control nuclei in the brain increase in size during mating season.[68] Among birds, changes in brain morphology to influence song patterns, frequency, and volume are common.[73] Gonadotropin-releasing hormone (GnRH) immunoreactivity, or the reception of the hormone, is lowered in European starlings exposed to longer periods of light during the day.[64][65]

The California sea hare, a gastropod, has more successful inhibition of egg-laying hormones outside of mating season due to increased effectiveness of inhibitors in the brain.[66] Changes to the inhibitory nature of regions of the brain can also be found in humans and other mammals.[67] In the amphibian Bufo japonicus, part of the amygdala is larger before breeding and during hibernation than it is after breeding.[69]

Seasonal brain variation occurs within many mammals. Part of the hypothalamus of the common ewe is more receptive to GnRH during breeding season than at other times of the year.[70] Humans experience a change in the "size of the hypothalamic suprachiasmatic nucleus and vasopressin-immunoreactive neurons within it"[67] during the fall, when these parts are larger. In the spring, both reduce in size.[74]

Traumatic brain injury research

Randy Nudo's group found that if a small stroke (an infarction) is induced by obstruction of blood flow to a portion of a monkey's motor cortex, the part of the body that responds by movement moves when areas adjacent to the damaged brain area are stimulated. In one study, intracortical microstimulation (ICMS) mapping techniques were used in nine normal monkeys. Some underwent ischemic-infarction procedures and the others, ICMS procedures. The monkeys with ischemic infarctions retained more finger flexion during food retrieval and after several months this deficit returned to preoperative levels.[75] With respect to the distal forelimb representation, "postinfarction mapping procedures revealed that movement representations underwent reorganization throughout the adjacent, undamaged cortex."[75] Understanding of interaction between the damaged and undamaged areas provides a basis for better treatment plans in stroke patients. Current research includes the tracking of changes that occur in the motor areas of the cerebral cortex as a result of a stroke. Thus, events that occur in the reorganization process of the brain can be ascertained. Nudo is also involved in studying the treatment plans that may enhance recovery from strokes, such as physiotherapy, pharmacotherapy, and electrical-stimulation therapy.

Jon Kaas, a professor at Vanderbilt University, has been able to show "how somatosensory area 3b and ventroposterior (VP) nucleus of the thalamus are affected by longstanding unilateral dorsal-column lesions at cervical levels in macaque monkeys."[76] Adult brains have the ability to change as a result of injury but the extent of the reorganization depends on the extent of the injury. His recent research focuses on the somatosensory system, which involves a sense of the body and its movements using many senses. Usually, damage of the somatosensory cortex results in impairment of the body perception. Kaas' research project is focused on how these systems (somatosensory, cognitive, motor systems) respond with plastic changes resulting from injury.[76]

One recent study of neuroplasticity involves work done by a team of doctors and researchers at Emory University, specifically Dr. Donald Stein[77] and Dr. David Wright. This is the first treatment in 40 years that has significant results in treating traumatic brain injuries while also incurring no known side effects and being cheap to administer.[19] Dr. Stein noticed that female mice seemed to recover from brain injuries better than male mice, and that at certain points in the estrus cycle, females recovered even better. This difference may be attributed to different levels of progesterone, with higher levels of progesterone leading to the faster recovery from brain injury in mice. However, clinical trials showed progesterone offers no significant benefit for traumatic brain injury human patients.[78]

History

Origin

The term "plasticity" was first applied to behavior in 1890 by William James in The Principles of Psychology.[79] The first person to use the term neural plasticity appears to have been the Polish neuroscientist Jerzy Konorski.[2][80]

In 1793, Italian anatomist Michele Vicenzo Malacarne described experiments in which he paired animals, trained one of the pair extensively for years, and then dissected both. He discovered that the cerebellums of the trained animals were substantially larger. But these findings were eventually forgotten.[81] The idea that the brain and its function are not fixed throughout adulthood was proposed in 1890 by William James in The Principles of Psychology, though the idea was largely neglected.[79] Until around the 1970s, neuroscientists believed that brain's structure and function was essentially fixed throughout adulthood.[82]

The term has since seen broadly applied:
Given the central importance of neuroplasticity, an outsider would be forgiven for assuming that it was well defined and that a basic and universal framework served to direct current and future hypotheses and experimentation. Sadly, however, this is not the case. While many neuroscientists use the word neuroplasticity as an umbrella term it means different things to different researchers in different subfields ... In brief, a mutually agreed upon framework does not appear to exist.[83]

Research and discovery

In 1923, Karl Lashley conducted experiments on rhesus monkeys that demonstrated changes in neuronal pathways, which he concluded were evidence of plasticity. Despite this, and other research that suggested plasticity took place, neuroscientists did not widely accept the idea of neuroplasticity.

In 1945, Justo Gonzalo concluded from his research of brain dynamics, that, contrary to the activity of the projection areas, the "central" cortical mass (more or less equidistant from the visual, tactile and auditive projection areas), would be a "maneuvering mass", rather unspecific or multisensory, with capacity to increase neural excitability and re-organize the activity by means of plasticity properties.[84] He gives as a first example of adaptation, to see upright with reversing glasses in the Stratton experiment,[85] and specially, several first-hand brain injuries cases in which he observed dynamic and adaptive properties in their disorders, in particular in the inverted perception disorder [e.g., see pp 260–62 Vol. I (1945), p 696 Vol. II (1950)].[84] He stated that a sensory signal in a projection area would be only an inverted and constricted outline that would be magnified due to the increase in recruited cerebral mass, and re-inverted due to some effect of brain plasticity, in more central areas, following a spiral growth.[86]

Marian Diamond of the University of California, Berkeley, produced the first scientific evidence of anatomical brain plasticity, publishing her research in 1964.[87][1]

Other significant evidence was produced in the 1960s and after, notably from scientists including Paul Bach-y-Rita, Michael Merzenich along with Jon Kaas, as well as several others.[82][88]

In the 1960s, Paul Bach-y-Rita invented a device that was tested on a small number of people, and involved a person sitting in a chair, in which were embedded nubs that were made to vibrate in ways that translated images received in a camera, allowing a form of vision via [sensory substitution]].[12][89]

Studies in people recovering from stroke also provided support for neuroplasticity, as regions of the brain remained healthy could sometimes take over, at least in part, functions that had been destroyed; Shepherd Ivory Franz did work in this area.[90][91]

Eleanor Maguire documented changes in hippocampal structure associated with acquiring the knowledge of London's layout in local taxi drivers.[92][93][94] A redistribution of grey matter was indicated in London Taxi Drivers compared to controls. This work on hippocampal plasticity not only interested scientists, but also engaged the public and media worldwide.

Michael Merzenich is a neuroscientist who has been one of the pioneers of neuroplasticity for over three decades. He has made some of "the most ambitious claims for the field – that brain exercises may be as useful as drugs to treat diseases as severe as schizophrenia – that plasticity exists from cradle to the grave, and that radical improvements in cognitive functioning – how we learn, think, perceive, and remember are possible even in the elderly."[12] Merzenich's work was affected by a crucial discovery made by David Hubel and Torsten Wiesel in their work with kittens. The experiment involved sewing one eye shut and recording the cortical brain maps. Hubel and Wiesel saw that the portion of the kitten's brain associated with the shut eye was not idle, as expected. Instead, it processed visual information from the open eye. It was "…as though the brain didn't want to waste any 'cortical real estate' and had found a way to rewire itself."[12]

This implied neuroplasticity during the critical period. However, Merzenich argued that neuroplasticity could occur beyond the critical period. His first encounter with adult plasticity came when he was engaged in a postdoctoral study with Clinton Woosley. The experiment was based on observation of what occurred in the brain when one peripheral nerve was cut and subsequently regenerated. The two scientists micromapped the hand maps of monkey brains before and after cutting a peripheral nerve and sewing the ends together. Afterwards, the hand map in the brain that they expected to be jumbled was nearly normal. This was a substantial breakthrough. Merzenich asserted that, "If the brain map could normalize its structure in response to abnormal input, the prevailing view that we are born with a hardwired system had to be wrong. The brain had to be plastic."[12] Merzenich received the 2016 Kavli Prize in Neuroscience "for the discovery of mechanisms that allow experience and neural activity to remodel brain function."[95]

Running a program from Excel Basic and waiting for the results

I haven't used Excel Basic in a while, so I don't know if this code is still useful.  The last version of Excel I used did not allow you to run a program and wait for it to finish:  it only had the Shell command, which returned immediately.  The code below will allow you to run another program and wait for the results.  It uses functions in the Windows API (not .NET functions) to accomplish this.

Attribute VB_Name = "RW_App"
'Code Module:         RW_App.base
'Author:              David J Strumfels
'Last Revision:       1/1/00
'
'This module contains the function RunWaitApp, which is basically a version of the
'VB Shell() command, in which the calling program waits for the shelled program to
'complete before returning.  In addition to the same lpCommandLine and
'wShowWindow arguments that Shell() takes, RunWaitApp also takes the boolean
'argument bWait, which determines whether the calling program will continue to have
'its events processed while lpCommandLine executes.  If bWait is False, the caller
'has events processed; if bWait is True and lWaitTime is a sufficiently large number,
'the caller is completely suspended, with no event processing at all.

'This is a little confusing, so NOTE:  RunWaitApp ALWAYS waits for lpCommandLine to
'complete before returning.  All that bWait does is determine whether caller events
'are always processed or not; that is, whether any caller windows are repainted,
'moved, or resized, or menu selections processed, or any other event-driven actions
'associated with the caller are processed.  If bWait is False, then the caller's
'events are always processed.  If bWait is True, then what happens depends on the
'value of lWaitTime:  if lWaitTime is very large -- essentially infinite -- the
'caller is completely frozen; if lWaitTime = 0, then this is equivalent to calling
'the function with bWait = False.

Option Explicit

Private Type PROCESS_INFORMATION
    hProcess As Long
    hThread As Long
    dwProcessId As Long
    dwThread As Long
End Type

Private Type STARTUPINFO
    cb As Long
    lpReserved As String
    lpDesktop As String
    dwX As Long
    dwY As Long
    dwXSize As Long
    dwYSize As Long
    dwXCountChars As Long
    dwYCountChars As Long
    dwFillAttribute As Long
    dwFlags As Long
    wShowWindow As Integer
    cbReserved2 As Long
    lpReserved2 As Long
    hStdInput As Long
    hStdOutput As Long
    hStdError As Long
End Type

Declare Function CreateProcess Lib "Kernel32" Alias "CreateProcessA" _
                                 (ByVal lpApplicationName As String, _
                                  ByVal lpCommandLine As String, _
                                  ByVal lpProcessAttributes As Long, _
                                  ByVal lpThreadAttributes As Long, _
                                  ByVal bInheritHandles As Long, _
                                  ByVal dwCreationFlags As Long, _
                                  lpEnvironment As Any, _
                                  ByVal lpCurrentDirectory As String, _
                                  lpStartupInfo As STARTUPINFO, _
                                  lpProcessInformation As PROCESS_INFORMATION) As Long

Private Declare Function CloseHandle Lib "Kernel32" (ByVal hObject As Long) As Long

Private Declare Function WaitForSingleObject Lib "Kernel32" _
                                  (ByVal hHandle As Long, _
                                   ByVal dwMilliseconds As Long) As Long
                                  
Declare Function FindExecutable Lib "Shell32.dll" Alias "FindExecutableA" _
                                  (ByVal lpFile As String, _
                                   ByVal lpDirectory As String, _
                                   ByVal lpResult As String) As Long
                                  
Function ShellWaitApp(lpFile As String, _
                      lpParameters As String, _
                      wShowWindow As Integer, _
                      bWait As Boolean, Optional lWaitTime As Long) As Boolean

  Dim lpResult As String * 255, lpCommandLine As String
  Dim res As Long
 
  res = FindExecutable(lpFile, CurDir, lpResult)
 
  If res <> 0 Then
    lpCommandLine = Left(lpResult, InStr(lpResult, Chr(0)) - 1) & " " & lpFile & " " & lpParameters
   
    If RunWaitApp(lpCommandLine, wShowWindow, bWait, lWaitTime) Then
      ShellWaitApp = True
    Else
      ShellWaitApp = False
    End If
     
  Else
    ShellWaitApp = False
  End If
 
End Function

Function RunWaitApp(lpCommandLine As String, _
                    wShowWindow As Integer, _
                    bWait As Boolean, Optional lWaitTime As Long) As Boolean
   
  Dim sinfo As STARTUPINFO
  Dim pinfo As PROCESS_INFORMATION
  Dim res As Long
  Dim lWait As Long

  If bWait Then
    lWait = lWaitTime
  Else
    Shell lpCommandLine, wShowWindow
    RunWaitApp = True
    Exit Function
  End If


  sinfo.cb = Len(sinfo)
  sinfo.wShowWindow = wShowWindow

  res = CreateProcess(vbNullString, _
                      lpCommandLine, _
                      0, 0, True, &H20, ByVal 0&, _
                      vbNullString, sinfo, pinfo)
                     
  If res <> 0 Then
 
    Do
      res = WaitForSingleObject(pinfo.hProcess, lWait)
     
      If res <> &H102& Then
        Exit Do
      End If

      DoEvents
    Loop While True
   
    CloseHandle pinfo.hProcess
    RunWaitApp = True
  Else
    RunWaitApp = False
  End If
 
End Function


Figuring out if a number is divisible by eleven.

You may know that, to determine if a number is divisible by three, you sum the digits and if the result is divisible by three the original number is. Same is true for nine.

This set me to wondering. We use base-10 arithmetic, and 9 is 1 less than 10. I'm not a mathematician but something yanked at my intuition here, so I wondered if there was a similar formula for eleven.
Indeed there is! Take the first digit of the test number, subtract the second, add the third, subtract the fourth, etc., etc., and if the resulting sum/difference is a multiple of eleven (including zero and negative numbers), the original number is divisible by eleven as well.

I can't prove this (in fact, I figured it out by brute force), but can only say it's worked in every case I've tried. I suspect that there are formulas for all numbers (say, seven or thirteen), but I'm at a loss what they would be, and I'm not inclined to beat my head against that wall.

Anyone have anything to contribute here?

Inequality (mathematics)

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Inequality...