The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, commonly called the Beers List, are guidelines for healthcare professionals to help improve the safety of prescribing medications for older adults 65 years and older in all except palliative setting.
They emphasize deprescribing medications that are unnecessary, which helps to reduce the problems of polypharmacy, drug interactions, and adverse drug reactions, thereby improving the risk–benefit ratio of medication regimens in at-risk people.
The criteria are used in geriatrics clinical care to monitor and improve the quality of care. They are also used in training, research, and healthcare policy to assist in developing performance measures and document outcomes. These criteria include lists of medications in which the potential risks may be greater than the potential benefits for people 65 and older. By considering this information, practitioners may be able to reduce harmful side effects caused by such medications. The Beers Criteria are intended to serve as a guide for clinicians and not as a substitute for professional judgement in prescribing decisions. The criteria may be used in conjunction with other information to guide clinicians about safe prescribing in older adults.
Brief History
Geriatrician Mark H. Beers formulated the Beers Criteria through a consensus panel of experts using the Delphi method. The criteria were originally published in the Archives of Internal Medicine in 1991 and updated in 1997, 2003, 2012, 2015, and most recently in January 2019.
In 2018, the American Geriatrics Society (AGS) partnered with CSIS Health Corp to provide the first and only licensed software application of the Beers Criteria for use in Electronic Health Records, Population Health Management, and Care Management platforms.
Management of Criteria
In 2011, the AGS convened an eleven-member multidisciplinary panel of experts in geriatric medicine, nursing, and pharmacotherapy to develop the 2012 edition of the AGS Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.
The 2012 AGS Beers Criteria differ from previous editions in several ways. In addition to using a modified Delphi process for building consensus, the expert panel followed the evidence-based approach that AGS has used since it developed its first practice guideline on persistent pain in 1998. The Institute of Medicine (IOM) in its 2011 report, Clinical Practice Guidelines We Can Trust, recommended that all guideline developers complete a systematic review of the evidence. Following the recommendation of the IOM, AGS added a public comment period that occurred in parallel to its standard invited external peer review process. In a significant departure from previous versions of the criteria, each recommendation is rated for quality of both the evidence supporting the panel’s recommendations and the strength of their recommendations.
In another departure from the 2003 criteria, the 2012 AGS Beers Criteria identify and group medications that may be inappropriate for older adults into three different categories instead of the previous two. The first category includes medications that are potentially inappropriate for older people because they either pose high risks of adverse effects or appear to have limited effectiveness in older patients, and because there are alternatives to these medications. The second category includes medications that are potentially inappropriate for older people who have certain diseases or disorders because these drugs may exacerbate the specified health problems. The third category includes medications that, although they may be associated with more risks than benefits in general, may be the best choice for a particular individual if administered with caution.
The 2012 AGS Beers Criteria was released in February 2012 via publication in the early online edition of the Journal of the American Geriatrics Society.
The most recent update to the Beers criteria was completed in 2019.
Style of the Publication
Drugs listed on the Beers List are categorised according to risks for negative outcomes. The tables include medications that have cautions, should be avoided, should be avoided with concomitant medical conditions, and are contraindicated and relatively contraindicated in the elderly population. An example of an included drug is diphenhydramine (Benadryl), a first-generation H1 antagonist with anticholinergic properties, which may increase sedation and lead to confusion or falls.
Evenly-suspended attention is the kind of direction-less listening – removed from both theoretical presuppositions and therapeutic goals – recommended by Sigmund Freud for use in psychoanalysis.
Outline
By attaching no preconceived importance to any particular part of the analyst’s discourse, and allowing their unconscious complete freedom to act, the analysand’s can best profit from the counterpart rule of free association on the part of the analysand.
Such “hovering” attention (as Freud put it in 1909 in the case of Little Hans) was a technical development on his part from the more aggressive listening and interpretation of the 1890s, as his shift from hypnosis to psychoanalysis took gradual shape.
Later Developments
Since Theodor Reik and his 1948 study Listening with the Third Ear, more analytic emphasis has been placed on the dialectic between evenly suspended attention, and the analyst’s cognitive working-over of what they hear. The part played by countertransference and by the analyst’s role responsiveness has also been highlighted.
Abstinence or the rule of abstinence is the principle of analytic reticence and/or frustration within a clinical situation.
It is a central feature of psychoanalytic theory – relating especially to the handling of the transference in analysis.
As Sigmund Freud wrote in 1914:
The cure must be carried through in abstinence. I mean by that not physical self-denial alone, nor the denial of every desire….But I want to state the principle that one must permit neediness and yearning to remain as forces favoring work and change.
Later Formulations
The validity of the abstinence principle has been rediscovered and re-affirmed in a variety of subsequent analytic traditions.
Jacques Lacan
Re-formulated the principle via the concept of ‘analytic bridge’ – the analyst necessarily playing the part of the unresponding dummy to bring the patient’s unconscious motivations out into the open.
Eric Berne
Saw analytic frustration as a means of avoiding playing a part in the patient’s life script.
R.D. Laing
In the context of the false self saw analytic abstinence operating in opposition to false self collusion: “It is in terms of basic frustration of the self’s search for a collusive complement for false identity that Freud’s dictum that analysis should be conducted under conditions of maximal frustration takes on its most cogent meaning”.
D.W. Winnicott
In the context of his notion of ‘holding’ the patient emphasised that understanding through verbal interpretation gave a deeper sense of holding than the physical act, use of which by the therapist could blur the symbolic nature of the analytic space.
Debates
The rule of abstinence has come under increasing challenge by Interpersonal and Intersubjective psychoanalysis, concerned about the inflexibility of the rule, and the way its relentless application may provoke unnecessary hostility, even an iatrogenic transference neurosis.
Defenders of the rule, against the practice of the warm supportive analyst, argue against the easy seductiveness of being overly ‘helpful’ in a self-defeating way already sketched out by Freud himself. The concept of optimal responsiveness – balancing frustration and gratification from moment to moment – offers some mediation in the dispute.
Affective neuroscience is the study of the neural mechanisms of emotion.
This interdisciplinary field combines neuroscience with the psychological study of personality, emotion, and mood. The putative existence of ‘basic emotions’ and their defining attributes represents a long lasting and yet unsettled issue in the field.
The term was coined by neuroscientist Jaak Panksepp, at a time when cognitive neuroscience focused on non-emotional cognition, such as attention or memory.
Brain Areas
Emotions are thought to be related to activity in brain areas that direct our attention, motivate our behaviour, and choose the significance of what is going on around us. Pioneering work by Paul Broca (1878), James Papez (1937), and Paul D. MacLean (1952) suggested that emotion is related to a group of structures in the centre of the brain called the limbic system, which includes the hypothalamus, cingulate cortex, hippocampi, and other structures. Research has shown that limbic structures are directly related to emotion, but other structures have been found to be of greater emotional relevance.
The following brain structures are currently thought to be involved in emotion:
Limbic System
Amygdala:
The amygdalae are two small, round structures located anterior to the hippocampi near the temporal poles.
The amygdalae are involved in detecting and learning which parts of our surroundings are important and have emotional significance.
They are critical for the production of emotion, and may be particularly so for negative emotions, especially fear.
Multiple studies have shown amygdala activation when perceiving a potential threat; various circuits allow the amygdala to use related past memories to better judge the possible threat.
Thalamus:
The thalamus is involved in relaying sensory and motor signals to the cerebral cortex, especially visual stimuli.
The thalamus plays an important role in regulating states of sleep and wakefulness.
Hypothalamus:
The hypothalamus is involved in producing a physical output associated with an emotion as well as in reward circuits.
Hippocampus:
The hippocampus is a structure of the medial temporal lobes that is mainly involved in memory.
It works to form new memories and also connects senses such as visual input, smell or sound to memories.
The hippocampus allows long term memories to be stored and retrieves them when necessary.
Memories are used within the amygdala to help evaluate stimulae.
Fornix:
The fornix is the main output pathway from the hippocampus to the mammillary bodies.
It has been identified as a main region in controlling spatial memory functions, episodic memory and executive functions.
Mammillary body:
Mammillary bodies are important for recollective memory.
Olfactory bulb:
The olfactory bulbs are the first cranial nerves, located on the ventral side of the frontal lobe.
They are involved in olfaction, the perception of odours.
Cingulate gyrus:
The cingulate gyrus is located above the corpus callosum and is usually considered to be part of the limbic system.
The parts of the cingulate gyrus have different functions, and are involved with affect, visceromotor control, response selection, skeletomotor control, visuospatial processing, and in memory access.
A part of the cingulate gyrus is the anterior cingulate cortex, which is thought to play a central role in attention and behaviourally demanding cognitive tasks.
It may be particularly important with regard to conscious, subjective emotional awareness.
This region of the brain may play an important role in the initiation of motivated behaviour.
The subgenual cingulate is more active during both experimentally induced sadness and during depressive episodes.
Other Brain Structures
Basal ganglia:
Basal ganglia are groups of nuclei found on either side of the thalamus.
Basal ganglia play an important role in motivation, action selection and reward learning.
Orbitofrontal cortex:
The orbitofrontal cortex is a major structure involved in decision making and the influence by emotion on that decision.
Prefrontal cortex:
The prefrontal cortex is the front of the brain, behind the forehead and above the eyes.
It appears to play a critical role in the regulation of emotion and behaviour by anticipating consequences.
It may play an important role in delayed gratification by maintaining emotions over time and organising behaviour toward specific goals.
Ventral striatum:
The ventral striatum is a group of subcortical structures thought to play an important role in emotion and behaviour.
One part of the ventral striatum called the nucleus accumbens is thought to be involved in the experience of pleasure.
Individuals with addictions experience increased activity in this area when they encounter the object of their addiction.
Insula:
The insular cortex is thought to play a critical role in the bodily experience of emotion, as it is connected to other brain structures that regulate the body’s autonomic functions (heart rate, breathing, digestion, etc.).
The insula is implicated in empathy and awareness of emotion.
Cerebellum:
A “Cerebellar Cognitive Affective Syndrome” has been described.
Both neuroimaging studies as well as studies following pathological cerebellar lesions (such as a stroke) demonstrate that the cerebellum has a significant role in emotional regulation.
Lesion studies have shown that cerebellar dysfunction can attenuate the experience of positive emotions.
While these same studies do not show an attenuated response to frightening stimuli, the stimuli did not recruit structures that normally would be activated (such as the amygdala).
Rather, alternative structures were activated, such as the ventromedial prefrontal cortex, the anterior cingulate gyrus, and the insula.
This may indicate that evolutionary pressure resulted in the development of the cerebellum as a redundant fear-mediating circuit to enhance survival.
It may also indicate a regulatory role for the cerebellum in the neural response to rewarding stimuli, such as money, drugs of abuse, and orgasm.
Lateral prefrontal cortex.
Primary sensorimotor cortex.
Temporal cortex.
Brainstem.
Right Hemisphere
The right hemisphere has been proposed as directly involved in emotion processing. Scientific theory regarding its role produced several models of emotional functioning. C.K. Mills was an early researcher who proposed a direct link between the right hemisphere and emotion processing, having observed decreased emotion processing in patients with lesions to the right hemisphere. In the late 1980s to early 1990s neocortical structures were shown to have an involvement in emotion. These findings led to the development of the right hemisphere hypothesis and the valence hypothesis.
Right Hemisphere Hypothesis
The right hemisphere hypothesis asserts that the right hemisphere is specialized for the expression and perception of emotion. It has been linked with mental strategies that are nonverbal, synthetic, integrative, holistic, and gestaltic. The right hemisphere is more in touch with subcortical systems of autonomic arousal and attention as demonstrated in patients that have increased spatial neglect when damage affects the right brain versus the left brain. Right hemisphere pathologies have been linked with abnormal patterns of autonomic nervous system responses. These findings would help signify the strong connection of the subcortical brain regions to the right hemisphere.
Valence Hypothesis
The valence hypothesis acknowledges the right hemisphere’s role in emotion, but asserts that it is mainly focused on the processing of negative emotions whereas the left hemisphere processes positive emotions. The two hemispheres have been the subject of much debate. One version states that the right hemisphere processes negative emotion leaving positive emotion to the left brain. A second version suggests that the right hemisphere predominates in experiencing both positive and negative emotion. More recently, the frontal lobe has been the focus of research, asserting that the frontal lobes of both hemispheres are involved in emotions, while the parietal and temporal lobes are involved in the processing of emotion. Decreased right parietal lobe activity has been associated with depression and increased right parietal lobe activity with anxiety arousal. The increasing understanding of the different hemispheres has led to increasingly complicated models, all based on the original valence model.
Cognitive Neuroscience
Despite their interactions, the study of cognition until the late 1990s, excluded emotion and focused on non-emotional processes (e.g. memory, attention, perception, action, problem solving and mental imagery). The study of the neural basis of non-emotional and emotional processes emerged as two separate fields: cognitive neuroscience and affective neuroscience. Emotional and non-emotional processes often involve overlapping neural and mental mechanisms.
Cognitive Neuroscience Tasks in Affective Neuroscience Research
Emotion Go/No-Go
The emotion go/no-go task has been used to study behavioural inhibition, particularly emotional modulation of this inhibition. A derivation of the original go/no-go paradigm, this task involves a combination of affective “go cues”, where the participant must rapidly make a motor response, and affective “no-go cues,” where a response must be withheld. Because “go cues” are more common, the task measures a subject’s ability to inhibit a response under different emotional conditions.
The task is common in tests of emotion regulation, and is often paired with neuroimaging measures to localize relevant brain function in both healthy individuals and those with affective disorders. For example, go/no-go studies converge with other methodology to implicate areas of the prefrontal cortex during inhibition of emotionally valenced stimuli.
Emotional Stroop
The emotional Stroop task, an adaptation to the original Stroop, measures attentional bias to emotional stimuli. Participants must name the ink colour of presented words while ignoring the words’ meanings. In general, participants have more difficulty detaching attention from affectively valenced words, than neutral words. This interference from valenced words is measured by the response latency in naming the colour of neutral words as compared with emotional words.
This task has been often used to test selective attention to threatening and other negatively valenced stimuli, most often in relation to psychopathology. Disorder-specific attentional biases have been found for a variety of mental disorders. For example, participants with spider phobia show a bias to spider-related words but not other negatively valenced words. Similar findings have been attributed to threat words related to other anxiety disorders. However, other studies have questioned these findings. In fact, anxious participants in some studies show the Stroop interference effect for both negative and positive words, when the words are matched for emotionality. This means that the specificity effects for various disorders may be largely attributable to the semantic relation of the words to the concerns of the disorder, rather than their emotionality.
Ekman 60 Faces Task
The Ekman faces task is used to measure emotion recognition of six basic emotions. Black and white photographs of 10 actors (6 male, 4 female) are presented, with each actor displaying each emotion. Participants are usually asked to respond quickly with the name of the displayed emotion. The task is a common tool to study deficits in emotion regulation in patients with dementia, Parkinson’s, and other cognitively degenerative disorders. The task has been used to analyse recognition errors in disorders such as borderline personality disorder, schizophrenia, and bipolar disorder.
Dot Probe (Emotion)
The emotional dot-probe paradigm is a task used to assess selective visual attention to and failure to detach attention from affective stimuli. The paradigm begins with a fixation cross at the centre of a screen. An emotional stimulus and a neutral stimulus appear side by side, after which a dot appears behind either the neutral stimulus (incongruent condition) or the affective stimulus (congruent condition). Participants are asked to indicate when they see this dot, and response latency is measured. Dots that appear on the same side of the screen as the image the participant was looking at will be identified more quickly. Thus, it is possible to discern which object the participant was attending to by subtracting the reaction time to respond to congruent versus incongruent trials.
The best documented research with the dot probe paradigm involves attention to threat related stimuli, such as fearful faces, in individuals with anxiety disorders. Anxious individuals tend to respond more quickly to congruent trials, which may indicate vigilance to threat and/or failure to detach attention from threatening stimuli. A specificity effect of attention has also been noted, with individuals attending selectively to threats related to their particular disorder. For example, those with social phobia selectively attend to social threats but not physical threats. However, this specificity may be even more nuanced. Participants with obsessive-compulsive disorder symptoms initially show attentional bias to compulsive threat, but this bias is attenuated in later trials due to habituation to the threat stimuli.
Fear Potentiated Startle
Fear-potentiated startle (FPS) has been utilised as a psychophysiological index of fear reaction in both animals and humans. FPS is most often assessed through the magnitude of the eyeblink startle reflex, which can be measured by electromyography. This eyeblink reflex is an automatic defensive reaction to an abrupt elicitor, making it an objective indicator of fear. Typical FPS paradigms involve bursts of noise or abrupt flashes of light transmitted while an individual attends to a set of stimuli. Startle reflexes have been shown to be modulated by emotion. For example, healthy participants tend to show enhanced startle responses while viewing negatively valenced images and attenuated startle while viewing positively valenced images, as compared with neutral images.
The startle response to a particular stimulus is greater under conditions of threat. A common example given to indicate this phenomenon is that one’s startle response to a flash of light will be greater when walking in a dangerous neighbourhood at night than it would under safer conditions. In laboratory studies, the threat of receiving shock is enough to potentiate startle, even without any actual shock.
Fear potentiated startle paradigms are often used to study fear learning and extinction in individuals with posttraumatic stress disorder and other anxiety disorders. In fear conditioning studies, an initially neutral stimulus is repeatedly paired with an aversive one, borrowing from classical conditioning. FPS studies have demonstrated that post-traumatic stress disorder patients have enhanced startle responses during both danger cues and neutral/safety cues as compared with healthy participants.
Learning
Affect plays many roles during learning. Deep, emotional attachment to a subject area allows a deeper understanding of the material and therefore, learning occurs and lasts. The emotions evoked when reading in comparison to the emotions portrayed in the content affects comprehension. Someone who is feeling sad understands a sad passage better than someone feeling happy. Therefore, a student’s emotion plays an important role during the learning process.
Emotion can be embodied or perceived from words read on a page or in a facial expression. Neuroimaging studies using fMRI have demonstrated that the same area of the brain that is activated when feeling disgust is activated when observing another’s disgust. In a traditional learning environment, the teacher’s facial expression can play a critical role in language acquisition. Showing a fearful facial expression when reading passages that contain fearful tones facilitates students learning of the meaning of certain vocabulary words and comprehension of the passage.
Models
The neurobiological basis of emotion is still disputed. The existence of basic emotions and their defining attributes represents a long lasting and yet unsettled issue in psychology. The available research suggests that the neurobiological existence of basic emotions is still tenable and heuristically seminal, pending some reformulation.
Basic Emotions
These approaches hypothesize that emotion categories (including happiness, sadness, fear, anger, and disgust) are biologically basic. In this view, emotions are inherited, biologically based modules that cannot be separated into more basic psychological components. Models following this approach hypothesize that all mental states belonging to a single emotional category can be consistently and specifically localised to either a single brain region or a defined network of brain regions. Each basic emotion category also shares other universal characteristics: distinct facial behaviour, physiology, subjective experience and accompanying thoughts and memories.
Psychological Constructionist Approaches
This approach to emotion hypothesizes that emotions like happiness, sadness, fear, anger and disgust (and many others) are constructed mental states that occur when brain systems work together. In this view, networks of brain regions underlie psychological operations (e.g. language, attention, etc.) that interact to produce emotion, perception, and cognition. One psychological operation critical for emotion is the network of brain regions that underlie valence (feeling pleasant/unpleasant) and arousal (feeling activated and energised). Emotions emerge when neural systems underlying different psychological operations interact (not just those involved in valence and arousal), producing distributed patterns of activation across the brain. Because emotions emerge from more basic components, heterogeneity affects each emotion category; for example, a person can experience many different kinds of fear, which feel differently, and which correspond to different neural patterns in the brain.
Meta-Analyses
A meta-analysis is a statistical approach to synthesizing results across multiple studies. Included studies investigated healthy, unmedicated adults and that used subtraction analysis to examine brain areas that were more active during emotional processing than during a neutral (control) condition.
Phan et al. 2002
In the first neuroimaging meta-analysis of emotion, Phan et al. (2002) analysed the results of 55 peer reviewed studies between January 1990 and December 2000 to determine if the emotions of fear, sadness, disgust, anger, and happiness were consistently associated with activity in specific brain regions. All studies used fMRI or PET techniques to investigate higher-order mental processing of emotion (studies of low-order sensory or motor processes were excluded). The authors’ tabulated the number of studies that reported activation in specific brain regions. For each brain region, statistical chi-squared analysis was conducted. Two regions showed a statistically significant association. In the amygdala, 66% of studies inducing fear reported activity in this region, as compared to ~20% of studies inducing happiness, ~15% of studies inducing sadness (with no reported activations for anger or disgust). In the subcallosal cingulate, 46% of studies inducing sadness reported activity in this region, as compared to ~20% inducing happiness and ~20% inducing anger. This pattern of clear discriminability between emotion categories was in fact rare, with other patterns occurring in limbic regions, paralimbic regions, and uni/heteromodal regions. Brain regions implicated across discrete emotion included the basal ganglia (~60% of studies inducing happiness and ~60% of studies inducing disgust reported activity in this region) and medial prefrontal cortex (happiness ~60%, anger ~55%, sadness ~40%, disgust ~40%, and fear ~30%).
Murphy et al. 2003
Murphy, et al. 2003 analysed 106 peer reviewed studies published between January 1994 and December 2001 to examine the evidence for regional specialisation of discrete emotions (fear, disgust, anger, happiness and sadness) across a larger set of studies. Studies included in the meta-analysis measured activity in the whole brain and regions of interest (activity in individual regions of particular interest to the study). 3-D Kolmogorov-Smirnov (KS3) statistics were used to compare rough spatial distributions of 3-D activation patterns to determine if statistically significant activations were specific to particular brain regions for all emotional categories. This pattern of consistently activated, regionally specific activations was identified in four brain regions: amygdala with fear (~40% of studies), insula with disgust (~70%), globus pallidus with disgust (~70%), and lateral orbitofrontal cortex with anger (80%). Other regions showed different patterns of activation across categories. For example, both the dorsal medial prefrontal cortex and the rostral anterior cingulate cortex showed consistent activity across emotions (happiness ~50%, sadness ~50%, anger ~ 40%, fear ~30%, and disgust ~ 20%).
Barrett et al. 2006
Barrett, et al. 2006 examined 161 studies published between 1990 and 2001. The authors compared the consistency and specificity of prior meta-analytic findings specific to each notional basic emotion. Consistent neural patterns were defined by brain regions showing increased activity for a specific emotion (relative to a neutral control condition), regardless of the method of induction used (for example, visual vs. auditory cue). Specific neural patterns were defined as separate circuits for one emotion vs. the other emotions (for example, the fear circuit must be discriminable from the anger circuit, although both may include common brain regions). In general, the results supported Phan et al. and Murphy et al., but not specificity. Consistency was determined through the comparison of chi-squared analyses that revealed whether the proportion of studies reporting activation during one emotion was significantly higher than the proportion of studies reporting activation during the other emotions. Specificity was determined through the comparison of emotion-category brain-localizations by contrasting activations in key regions that were specific to particular emotions. Increased amygdala activation during fear was the most consistently reported across induction methods (but not specific). Both meta-analyses associated the anterior cingulate cortex with sadness, although this finding was less consistent (across induction methods) and was not specific. Both meta-analyses found that disgust was associated with the basal ganglia, but these findings were neither consistent nor specific. Neither consistent nor specific activity was observed across the meta-analyses for anger or happiness. This meta-analysis introduced the concept of the basic, irreducible elements of emotional life as dimensions such as approach and avoidance.
Kober et al. 2008
Kober, et al. 2008 reviewed 162 neuroimaging studies published between 1990-2005 to determine if groups of brain regions showed consistent activation patterns while experiencing an emotion directly and (indirectly) as experienced by another. This analysis used multilevel kernel density analysis (MKDA) to examine fMRI and PET studies, a technique that prevents single studies from dominating the results (particularly if they report multiple nearby peaks) and that enables studies involving more participants to exert more influence upon the results. MKDA was used to establish a neural reference space that includes the set of regions showing consistent increases across all studies. This neural reference space was partitioned into functional groups of brain regions showing similar activation patterns by using multivariate techniques to determine co-activation patterns and then using data-reduction techniques to define the functional groupings, resulting in six groups. The authors discussed each functional group in terms of more basic psychological operations.
Group
Regions
Notes
Core Limbic
Left amygdala, hypothalamus, periaqueductal gray/thalamus regions, and amygdala/ventral striatum/ventral globus pallidus/thalamus regions.
Integrative emotional centre that plays a general role in evaluating affective significance.
Lateral Paralimbic
Ventral anterior insula/frontal operculum/right temporal pole/ posterior orbitofrontal cortex, the anterior insula/ posterior orbitofrontal cortex, the ventral anterior insula/ temporal cortex/ orbitofrontal cortex junction, the midinsula/ dorsal putamen, and the ventral striatum /mid insula/ left hippocampus.
Plays a role in motivation, contributing to the general valuation of stimuli and particularly in reward.
Plays a role in both the generation and regulation of emotion.
Cognitive/ Motor Network
Right frontal operculum, the right interior frontal gyrus, and the pre-supplementray motor area/ left interior frontal gyrus, regions.
Not specific to emotion, but instead appear to play a more general role in information processing and cognitive control.
Occipital/ Visual Association
V8 and V4 areas of the primary visual cortex, the medial temporal lobe, and the lateral occipital cortex.
Medial Posterior
Posterior cingulate cortex and area V1 of the primary visual cortex.
The authors suggest that these regions play a joint role in visual processing and attention to emotional stimuli.
Vytal et al. 2010
Vytal, et al. 2010 examined 83 neuroimaging studies published between 1993-2008 to examine whether neuroimaging evidence supports biologically discrete, basic emotions (i.e. fear, anger, disgust, happiness, and sadness). Consistency analyses identified brain regions associated with individual emotions. Discriminability analyses identified brain regions that were differentially active under contrasting pairs of emotions. This meta-analysis examined PET or fMRI studies that reported whole brain analyses identifying significant activations for at least one of the five emotions relative to a neutral or control condition. The authors used activation likelihood estimation (ALE) to perform spatially sensitive, voxel-wise (sensitive to the spatial properties of voxels) statistical comparisons across studies. This technique allows for direct statistical comparison between activation maps associated with each discrete emotion. Thus, discriminability between the five discrete emotion categories was assessed on a more precise spatial scale than in prior meta-analyses.
Consistency was first assessed by comparing the cross-study ALE map for each emotion to ALE maps generated by random permutations. Discriminability was assessed by pair-wise contrasts of emotion maps. Consistent and discriminable activation patterns were observed for the five categories.
Emotion
Peak
Regions
Happiness
Right superior temporal gyrus, left rostral anterior cingulate cortex.
9 regional brain clusters.
Sadness
Left medial frontal gyrus.
35 clusters – especially, left medial frontal gyrus, right middle temporal gyrus, and right inferior frontal gyrus.
Anger
Left inferior frontal gyrus.
13 clusters – bilateral inferior frontal gyrus, and in right parahippocampal gyrus.
Fear
Left amygdala.
11 clusters – left amygdala and left putamen.
Disgust
Right insula/right inferior frontal gyrus.
16 clusters – right putamen and the left insula.
Lindquist et al. 2012
Lindquist, et al. reviewed 91 PET and fMRI studies published between January 1990 and December 2007. The studies used induction methods that elicit emotion experience or emotion perception of fear, sadness, disgust, anger, and happiness. The goal was to compare basic emotions approaches with psychological constructionist approaches. A MKDA transformed the individual peak into a neural reference space. The density analysis was then used to identify voxels with more consistent activations for a specific emotion category than all other emotions. Chi-squared analysis was used to create statistical maps that indicated whether each previously identified and consistently active region was more frequently activated in studies of each emotion category than average, regardless of activations elsewhere in the brain. Chi-squared analysis and density analysis both defined functionally consistent and selective regions (regions that showed a more consistent activity increase) for one emotion category. Thus, a selective region could present increased activations to multiple emotions, as long as the response to one emotion was relatively stronger.
A series of logistic regressions were performed to identify regions that while consistent and selective to an emotion were additionally specific to that emotion. Specificity was defined as showing increased activations for only one emotional category. Strong support for basic emotions was defined as evidence that brain areas respond to only one emotional category. Strong support for the constructionist approach was defined as evidence that psychological operations consistently occur across many brain regions and multiple emotional categories.
The results indicated that many brain regions demonstrated consistent and selective activations in the experience or perception of one emotion category. Consistent with constructionist models, however, no region demonstrated functional specificity for the emotions of fear, disgust, happiness, sadness or anger.
The authors proposed different roles for the brain regions that have traditionally been associated with only one emotion category. The authors propose that the amygdala, anterior insula, orbitofrontal cortex each contribute to “core affect,” which are basic feelings that are pleasant or unpleasant with some level of arousal.
Region
Role
Amygdala
Indicating whether external sensory information is motivationally salient, novel and/or evokes uncertainty.
Anterior Insula
Represents core affective feelings in awareness across emotion categories, driven largely by body sensations.
Orbitofrontal Cortex
Functions as a site for integrating sensory information from the body and the world to guide behaviour.
Closely related to core affect, the authors propose that the anterior cingulate and dorsolateral prefrontal cortex play vital roles in attention. The anterior cingulate supports the use of sensory information for directing attention and motor responses during response selection while the dorsolateral prefrontal cortex supporting executive attention. In many psychological construction approaches, emotions relate an individual’s situation in the world to internal body states, referred to as “conceptualisation”. The dorsomedial prefrontal cortex and hippocampus were consistently active in this context: regions that play an important role conceptualising are also involved in simulating previous experience (e.g. knowledge, memory). Language is also central to conceptualising, and regions that support language, including ventrolateral prefrontal cortex, were also consistently active across studies of emotion experience and perception.
In the psychology of defence mechanisms and self-control, acting out is the performance of an action considered bad or anti-social. In general usage, the action performed is destructive to self or to others.
The term is used in this way in sexual addiction treatment, psychotherapy, criminology and parenting. In contrast, the opposite attitude or behaviour of bearing and managing the impulse to perform one’s impulse is called acting in.
The performed action may follow impulses of an addiction (e.g. drinking, drug taking or shoplifting). It may also be a means designed (often unconsciously or semi-consciously) to garner attention (e.g. throwing a tantrum or behaving promiscuously). Acting out may inhibit the development of more constructive responses to the feelings in question.
In Analysis
Sigmund Freud considered that patients in analysis tended to act out their conflicts in preference to remembering them – repetition compulsion. The analytic task was then to help “the patient who does not remember anything of what he has forgotten and repressed, but acts it out” to replace present activity by past memory.
Otto Fenichel added that acting out in an analytic setting potentially offered valuable insights to the therapist; but was nonetheless a psychological resistance in as much as it deals only with the present at the expense of concealing the underlying influence of the past. Lacan also spoke of “the corrective value of acting out”, though others qualified this with the proviso that such acting out must be limited in the extent of its destructive/self-destructiveness.
Annie Reich pointed out that the analyst may use the patient by acting out in an indirect countertransference, for example to win the approval of a supervisor.
Interpretations
The interpretation of a person’s acting out and an observer’s response varies considerably, with context and subject usually setting audience expectations.
In Parenting
Early years, temper tantrums can be understood as episodes of acting out. As young children will not have developed the means to communicate their feelings of distress, tantrums prove an effective and achievable method of alerting parents to their needs and requesting attention.
As children develop they often learn to replace these attention-gathering strategies with more socially acceptable and constructive communications. In adolescent years, acting out in the form of rebellious behaviours such as smoking, shoplifting and drug use can be understood as “a cry for help.” Such pre-delinquent behaviour may be a search for containment from parents or other parental figures. The young person may seem to be disruptive – and may well be disruptive – but this behaviour is often underpinned by an inability to regulate emotions in some other way.
In Addiction
In behavioural or substance addiction, acting out can give the addict the illusion of being in control. Many people who suffer with addiction, either refuse to admit they struggle with it, or some do not even realise they have an addiction. For most people, when their addiction is addressed, they become defensive and act out. This can be a result of multiple emotions including shame, fear of judgement, or anger. It is important to be patient and understanding towards those who suffer with addiction, and to realise that most people want to break free from the symptoms and baggage that come with addiction, but do not know how or where to start. Thankfully, there are many preventative measures and programs than can help those who personally struggle with addiction, or for those who have a friend or family member that suffers with addiction.
In Criminology
Criminologists debate whether juvenile delinquency is a form of acting out, or rather reflects wider conflicts involved in the process of socialisation. Deviant behaviour is commonly associated with crime and social deviance. Many of those who are involved in crime, usually grew up in broken homes, or had no authority figure in their life. For some, a life of crime is all they have ever known. This could be a reason as to why there is a debate over whether or not juvenile delinquency is a form of acting out.
Alternatives
Acting out painful feelings may be contrasted with expressing them in ways more helpful to the sufferer, e.g. by talking out, expressive therapy, psychodrama or mindful awareness of the feelings. Developing the ability to express one’s conflicts safely and constructively is an important part of impulse control, personal development and self-care.
“Acting in” is a psychological term which has been given various meanings over the years, but which is most generally used in opposition to acting out to cover conflicts which are brought to life inside therapy, as opposed to outside.
One commentator, noting the variety of usages, points out that it is often “unclear whether ‘in’ refers to the internalisation into the personality, to the growth in insight, or to the acting within the session”.
Patients
With respect to patients, the term ‘acting in’ has been used to refer to the process of a client/patient bringing an issue from outside the therapy into the analytic situation, and acting upon it there.
The therapist is advised to respond to the issue immediately to prevent further and more disruptive acting in.
Hanna Segal distinguished positive acting in from destructive acting in – both being aimed however at affecting the analyst’s state of mind, whether to communicate or to confuse.
Posture
The term was used in 1957 by Meyer A. Zeligs to refer specifically to the postures taken by analysts in a psychoanalytic session.
Therapists
Psychoanalysis also describes as ‘acting in’ the process whereby the analyst brings his or her personal countertransference into the analytic situation – as opposed to the converse, the acting out of the patient’s transference.
The result is generally agreed to produce a chaotic analytic situation which hampers therapeutic progress.
The term was used rather differently however by Carl Whitaker in the 60’s, so as to refer to the technique whereby therapists increase their involvement in a session in such a way as to ramp up the patient’s anxiety for therapeutic ends.
Inhibitory control, also known as response inhibition, is a cognitive process – and more specifically an executive function – that permits an individual to inhibit their impulses and natural, habitual, or dominant behavioural responses to stimuli (e.g. prepotent responses) in order to select a more appropriate behaviour that is consistent with completing their goals.
Self-control is an important aspect of inhibitory control. For example, successfully suppressing the natural behavioural response to eat cake when one is craving it while dieting requires the use of inhibitory control.
The prefrontal cortex, caudate nucleus, and subthalamic nucleus are known to regulate inhibitory control cognition. Inhibitory control is impaired in both addiction and attention deficit hyperactivity disorder. In healthy adults and ADHD individuals, inhibitory control improves over the short term with low (therapeutic) doses of methylphenidate or amphetamine. Inhibitory control may also be improved over the long-term via consistent aerobic exercise.
Tests
An inhibitory control test is a neuropsychological test that measures an individual’s ability to override their natural, habitual, or dominant behavioural response to a stimulus in order to implement more adaptive goal-oriented behaviours. Some of the neuropsychological tests that measure inhibitory control include the Stroop task, go/no-go task, Simon task, Flanker task, anti-saccade tasks, delay of gratification tasks, and stop-signal tasks.
Gender Differences
Females tend to have a greater basal capacity to exert inhibitory control over undesired or habitual behaviours and respond differently to modulatory environmental contextual factors relative to males. For example, listening to music tends to significantly improve the rate of response inhibition in females, but reduces the rate of response inhibition in males.
Living Is For Everyone (LIFE) is a suicide prevention initiative of the Australian Government’s National Suicide Prevention Strategy (NSPS).
Background
The National Suicide Prevention Strategy funds a number of programmes, some jointly funded with the National Mental Health Strategy.
The programmes, which operate in a range of settings, use population-based approaches with an emphasis on community capacity building.
The LIFE initiative has two main components:
The LIFE resources; and
The LIFE website.
The LIFE resources were redeveloped from a 2000 document and published in 2008. They are designed for people working with those at risk of suicide, with the broad intention of reducing the rate at which people take their own lives in Australia.
The LIFE resources have three components:
The LIFE Framework: The Australian reference for suicide prevention activities;
LIFE Research and Evidence: A review of statistics, trends, comparisons and issues in suicide and self-harm prevention; and
LIFE fact sheets: A set of 24 fact sheets that provide summaries and advice about suicide prevention.
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures.
Any medications within the family of neuroleptics can cause the condition, though typical antipsychotics appear to have a higher risk than atypicals, specifically first generation antipsychotics like haloperidol. Onset is often within a few weeks of starting the medication but can occur at any time. Risk factors include dehydration, agitation, and catatonia.
Rapidly decreasing the use of levodopa or other dopamine agonists, such as pramipexole, may also trigger the condition. The underlying mechanism involves blockage of dopamine receptors. Diagnosis is based on symptoms.
Management includes stopping the offending medication, rapid cooling, and starting other medications. Medications used include dantrolene, bromocriptine, and diazepam. The risk of death among those affected is about 10%. Rapid diagnosis and treatment is required to improve outcomes. Many people can eventually be restarted on a lower dose of antipsychotic.
As of 2011, among those in psychiatric hospitals on neuroleptics about 15 per 100,000 are affected per year (0.015%). In the second half of the 20th century rates were over 100 times higher at about 2% (2,000 per 100,000). Males appear to be more often affected than females. The condition was first described in 1956.
Brief History
NMS was known about as early as 1956, shortly after the introduction of the first phenothiazines. NMS was first described in 1960 by French clinicians who had been working on a study involving haloperidol. They characterized the condition that was associated with the side effects of haloperidol “syndrome malin des neuroleptiques”, which was translated to neuroleptic malignant syndrome.
Signs and Symptoms
The first symptoms of neuroleptic malignant syndrome are usually muscle cramps and tremors, fever, symptoms of autonomic nervous system instability such as unstable blood pressure, and sudden changes in mental status (agitation, delirium, or coma). Once symptoms appear, they may progress rapidly and reach peak intensity in as little as three days. These symptoms can last anywhere from eight hours to forty days.
Symptoms are sometimes misinterpreted by doctors as symptoms of mental illness which can result in delayed treatment. NMS is less likely if a person has previously been stable for a period of time on antipsychotics, especially in situations where the dose has not been changed and there are no issues of noncompliance or consumption of psychoactive substances known to worsen psychosis.
Increased body temperature >38 °C (>100.4 °F);
Confused or altered consciousness;
sweating;
Rigid muscles; and/or
Autonomic imbalance.
Causes
NMS is usually caused by antipsychotic drug use, and a wide range of drugs can result in NMS. Individuals using butyrophenones (such as haloperidol and droperidol) or phenothiazines (such as promethazine and chlorpromazine) are reported to be at greatest risk. However, various atypical antipsychotics such as clozapine, olanzapine, risperidone, quetiapine, and ziprasidone have also been implicated in cases.
NMS may also occur in people taking dopaminergic drugs (such as levodopa) for Parkinson’s disease, most often when the drug dosage is abruptly reduced. In addition, other drugs with anti-dopaminergic activity, such as the antiemetic metoclopramide, can induce NMS. Tetracyclics with anti-dopaminergic activity have been linked to NMS in case reports, such as the amoxapines. Additionally, desipramine, dothiepin, phenelzine, tetrabenazine, and reserpine have been known to trigger NMS. Whether lithium can cause NMS is unclear.
At the molecular level, NMS is caused by a sudden, marked reduction in dopamine activity, either from withdrawal of dopaminergic agents or from blockade of dopamine receptors.
Risk Factors
One of the clearest risk factors in the development of NMS is the course of drug therapy chosen to treat a condition. Use of high-potency neuroleptics, a rapid increase in the dosage of neuroleptics, and use of long-acting forms of neuroleptics are all known to increase the risk of developing NMS.
It has been purported that there is a genetic risk factor for NMS, since identical twins have both presented with NMS in one case, and a mother and two of her daughters have presented with NMS in another case.
Demographically, it appears that males, especially those under forty, are at greatest risk for developing NMS, although it is unclear if the increased incidence is a result of greater neuroleptic use in men under forty. It has also been suggested that postpartum women may be at a greater risk for NMS.
An important risk factor for this condition is Lewy body dementia. These patients are extremely sensitive to neuroleptics. As a result, neuroleptics should be used cautiously in all cases of dementia.
Pathophysiology
The mechanism is commonly thought to depend on decreased levels of dopamine activity due to:
Dopamine receptor blockade.
Genetically reduced function of dopamine receptor D2.
It has been proposed that blockade of D2-like (D2, D3 and D4) receptors induce massive glutamate release, generating catatonia, neurotoxicity and myotoxicity. Additionally, the blockade of diverse serotonin receptors by atypical antipsychotics and activation of 5HT1 receptors by certain of them reduces GABA release and indirectly induces glutamate release, worsening this syndrome.
The muscular symptoms are most likely caused by blockade of the dopamine receptor D2, leading to abnormal function of the basal ganglia similar to that seen in Parkinson’s disease.
However, the failure of D2 dopamine receptor antagonism, or dopamine receptor dysfunction, do not fully explain the presenting symptoms and signs of NMS, as well as the occurrence of NMS with atypical antipsychotic drugs with lower D2 dopamine activity. This has led to the hypothesis of sympathoadrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) as a mechanism for NMS. Release of calcium is increased from the sarcoplasmic reticulum with antipsychotic usage. This can result in increased muscle contractility, which can play a role in the breakdown of muscle, muscle rigidity, and hyperthermia. Some antipsychotic drugs, such as typical neuroleptics, are known to block dopamine receptors; other studies have shown that when drugs supplying dopamine are withdrawn, symptoms similar to NMS present themselves.
There is also thought to be considerable overlap between malignant catatonia and NMS in their pathophysiology, the former being idiopathic and the latter being the drug-induced form of the same syndrome.
The raised white blood cell count and creatine phosphokinase (CPK) plasma concentration seen in those with NMS is due to increased muscular activity and rhabdomyolysis (destruction of muscle tissue). The patient may suffer hypertensive crisis and metabolic acidosis. A non-generalized slowing on an EEG is reported in around 50% of cases.
The fever seen with NMS is believed to be caused by hypothalamic dopamine receptor blockade. The peripheral problems (the high white blood cell and CPK count) are caused by the antipsychotic drugs. They cause an increased calcium release from the sarcoplasmic reticulum of muscle cells which can result in rigidity and eventual cell breakdown. No major studies have reported an explanation for the abnormal EEG, but it is likely also attributable to dopamine blockage leading to changes in neuronal pathways.
Diagnosis
Differential Diagnosis
Differentiating NMS from other neurological disorders can be very difficult. It requires expert judgement to separate symptoms of NMS from other diseases. Some of the most commonly mistaken diseases are encephalitis, toxic encephalopathy, status epilepticus, heat stroke, catatonia and malignant hyperthermia. Due to the comparative rarity of NMS, it is often overlooked and immediate treatment for the syndrome is delayed. Drugs such as cocaine and amphetamine may also produce similar symptoms.
The differential diagnosis is similar to that of hyperthermia, and includes serotonin syndrome. Features which distinguish NMS from serotonin syndrome include bradykinesia, muscle rigidity, and a high white blood cell count.
Treatment
NMS is a medical emergency and can lead to death if untreated. The first step is to stop the antipsychotic medication and treat the hyperthermia aggressively, such as with cooling blankets or ice packs to the axillae and groin. Supportive care in an intensive care unit capable of circulatory and ventilatory support is crucial. The best pharmacological treatment is still unclear. Dantrolene has been used when needed to reduce muscle rigidity, and more recently dopamine pathway medications such as bromocriptine have shown benefit. Amantadine is another treatment option due to its dopaminergic and anticholinergic effects. Apomorphine may be used however its use is supported by little evidence. Benzodiazepines may be used to control agitation. Highly elevated blood myoglobin levels can result in kidney damage, therefore aggressive intravenous hydration with diuresis may be required. When recognised early NMS can be successfully managed; however, up to 10% of cases can be fatal.
Should the affected person subsequently require an antipsychotic, trialling a low dose of a low-potency atypical antipsychotic is recommended.
Prognosis
The prognosis is best when identified early and treated aggressively. In these cases NMS is not usually fatal. In earlier studies the mortality rates from NMS ranged from 20%-38%, but by 2009 mortality rates were reported to have fallen below 10% over the previous two decades due to early recognition and improved management. Re-introduction to the drug that originally caused NMS to develop may also trigger a recurrence, although in most cases it does not.
Memory impairment is a consistent feature of recovery from NMS, and is usually temporary though in some cases may become persistent.
Epidemiology
Pooled data suggest the incidence of NMS is between 0.2%-3.23%. However, greater physician awareness coupled with increased use of atypical anti-psychotics have likely reduced the prevalence of NMS. Additionally, young males are particularly susceptible and the male-female ratio has been reported to be as high as 2:1.
Research
While the pathophysiology of NMS remains unclear, the two most prevalent theories are:
Reduced dopamine activity due to receptor blockade.
Sympathoadrenal hyperactivity and autonomic dysfunction.
In the past, research and clinical studies seemed to corroborate the D2 receptor blockade theory in which antipsychotic drugs were thought to significantly reduce dopamine activity by blocking the D2 receptors associated with this neurotransmitter. However, recent studies indicate a genetic component to the condition. In support of the sympathoadrenal hyperactivity model proposed, it has been hypothesized that a defect in calcium regulatory proteins within the sympathetic neurons may bring about the onset of NMS. This model of NMS strengthens its suspected association with malignant hyperthermia in which NMS may be regarded as a neurogenic form of this condition which itself is linked to defective calcium-related proteins.
The introduction of atypical antipsychotic drugs, with lower affinity to the D2 dopamine receptors, was thought to have reduced the incidence of NMS. However, recent studies suggest that the decrease in mortality may be the result of increased physician awareness and earlier initiation of treatment rather than the action of the drugs themselves. NMS induced by atypical drugs also resembles “classical” NMS (induced by “typical” antipsychotic drugs), further casting doubt on the overall superiority of these drugs.
Ikigai (生き甲斐, ‘a reason for being’) is a Japanese concept referring to something that gives a person a sense of purpose, a reason for living.
Meaning and Etymology
The Oxford English Dictionary defines ikigai, particularly with reference to Japanese culture, as “a motivating force; something or someone that gives a person a sense of purpose or a reason for living”. More generally it may refer to something that brings pleasure or fulfilment.
The term compounds two Japanese words: iki (生き, meaning ‘life; alive’) and kai (甲斐, meaning ‘(an) effect; (a) result; (a) fruit; (a) worth; (a) use; (a) benefit; (no, little) avail’) (sequentially voiced as gai), to arrive at ‘a reason for living [being alive]; a meaning for [to] life; what [something that] makes life worth living; a raison d’être’.
Overview
Ikigai can describe having a sense of purpose in life, as well as being motivated. According to a study,[vague] feeling ikigai as described in Japanese usually means the feeling of accomplishment and fulfilment that follows when people pursue their passions. Activities that allow one to feel ikigai are not forced on an individual; they are perceived as being spontaneous and undertaken willingly, therefore they are personal and depend on a person’s inner self.
According to psychologist Katsuya Inoue, ikigai is a concept consisting of two aspects: “sources or objects that bring value or meaning to life” and “a feeling that one’s life has value or meaning because of the existence of its source or object”. Inoue classifies ikigai into three directions – social ikigai, non-social ikigai, and anti-social ikigai – from a social perspective. Social ikigai refers to ikigai that are accepted by society through volunteer activities and circle activities. An asocial ikigai is an ikigai that is not directly related to society, such as faith or self-discipline. Anti-social ikigai refers to ikigai, which is the basic motivation for living through dark emotions, such as the desire to hate someone or something or to continue having a desire to revenge.
National Geographic reporter Dan Buettner suggested ikigai may be one of the reasons for the longevity of the people of Okinawa. According to Buettner, Okinawans have less desire to retire, as people continue to do their favourite job as long as they remain healthy. “Moai”, the close-knit friend group, is considered an important reason for the people of Okinawa to live long. In 2016, a book based on the concept, entitled ‘Ikigai: The Japanese Secret to a Long and Happy Life’, was published by Penguin Books, written by Héctor García and Francesc Miralles.
Early Popularisation
Although the concept of ikigai has long existed in Japanese culture, it was first popularised by Japanese psychiatrist and academic Mieko Kamiya in her 1966 book “On the Meaning of Life” (生きがいについて, ikigai ni tsuite). The book has not yet been translated into English.
Importance
In the 1960s, 1970s and 1980s, ikigai was thought to be experienced towards either the betterment of society (“subordinating one’s own desires to others”) or improvement of oneself (“following one’s own path”).
According to anthropologist Chikako Ozawa-de Silva, for an older generation in Japan, their ikigai was to “fit this standard mold of company and family”, whereas the younger generation reported their ikigai to be about “dreams of what they might become in the future”.
A 2012 study in the Global Journal of Health Science suggested that having the feeling of ikigai influenced the functioning of the frontal lobe. Some studies showed that people who do not feel ikigai are more likely to experience cardiovascular diseases. However, there was no evidence of any correlation with development of malignant tumours.
Mental Health Matters 
You must be logged in to post a comment.