Memory
1 MEMORY
1.1
Language
1.1.1
Functional segregation of language area via
sentence repetition
Repetition of sentences can segregate language area of the
brain via the functional significance. Two cluster in the left superior
temporal sulcus: identical repetition suppression whether the sentence is from
one same speaker or two different speakers. The homologous right regions
[excuse me? What?] are sensitive only if
the speaker voice is the same.
Syllable discrimination
Activation detected in left inferior frontal gyrus and
insula (also when metaphonologic task / syntactical processing => also known
as the same exact thing)
Functional segregation of cortical language areas by
sentence repetition dehaene-lambertz-al-fiac-hbm2006
1.1.2
Aphasia – impaired language ability
Aphasia is an impairment of language, affecting the
production or comprehension of speech and the ability to read or write. Aphasia
is always due to injury to the brain-most commonly from a stroke
1.1.3
Insula (Island of Reil)
The left insula is noticeably larger than the right in most
humans. The asymmetry and location in the epicenter of language area suggest
active in language processes. Insula damage is related to conduction aphasia;
Broca’s aphasia (anterior insula); Wernicke’s aphasia(word deaf = posterior
insula). Mutism often exhibit from
insular damage.
Motor planning of speech: left precentral gyrus of the
insula. = > articulatory movement planning deficits (apraxia of speech)
Learning grammar: explicit learning of artificial grammar
sequences s based in a circuit that
includes the insula as a key mediator.
Implicit learning of artificial grammar sequences: activated
frontal striatal circuit.
COGNITION results from the dynamic interaction of
distributed brain area operating in large scale networks. They refer to a
“Salience Network”, involved in monitoring the salience of external inputs and
internal brain events. The salience network is proposed to be anchored in
anterior insular and dorsal anterior cingulate cortices.
1.1.4
Insula connections loci mapping
Cluster 1 – claustrum (insular subcortical gray matter)
Extend focus subcortic and anterior to BA9, the middle
frontal gyrus in the prefrontal cortex. Involved in complex language process
like use of verbal strategy in executive efunction. BA44 the language
production, fluency, sequencing, grammar.
Cluster 2 – anterior cingulate gyrus (motor org, prep,
cognitive motor inhibition and language initiate); BA6 the medial frontal gyrus
including supplementary motor area involved to language initiation and
maintenance of voluntary speech production. Insula in the circuit to control
verbal initiative and maintain speech production.
Cluster 3 – right insula and claustrum.
Cluster 4 – left BA7 the superior parietal lobe involves
ideomotor praxis, motor imagery, motor learning, language process, temporal
context recognition.
Cluster 5 – BA37 posterior inferior temporal gyrus, middle
temporal gyrus, fusiform gyrus, cerebellar culmen.
2014 Ardila et al. Participation of the insula in language 2
xxxx
1.1.5
Insula processing skewness related uncertainty
in both object and subject manner. Anticipatory active
insula to object skew primary middle ventral region of insula. To subject skew
a dorsal region. Both implicated to interoceptive input and uncertainty related
signal frequently used for somatic marking supports. Left insula preferential
innervation by parasympathetic autonomic activity - approach behavior. Right
insula preferential innervation to sympathetic autonomic activity (craig 2009)
- departure from reware symmetry to motivate an increase of attention. Reward skewness coding in the insula
independent of probability and loss 2415.full
1.2
FRONTO AMYGDALA CIRCUIT
1.2.1
Pre Domination of Right Hemisphere
There is a misattribution of the
right hemisphere dominance in the recall of memory that has supported the
assumption and therapeutic method for study of emotionally traumatic memory
recall in a person. Neuro Images show
activation in the right hemisphere dominantly when the subject recalls
emotionally traumatic memory.
Emotionally Traumatic Memory
the emotion serves to make the subject feel traumatized AGAIN. And therefore,
the disruption of reaction and response to the real time environment. The
subject begins to respond to the environment as though prior conditions are not
longer dis-located but actively present in the environment. Hence, the Memory
is the cause of re-activation of emotions surrounding acute traumatization.
To repeal incorrect associations of the vocabulary and grammar: “emotionally
traumatic memory” it should be substituted and held to account for explicit
representation and disallow it to generalize itself into inapplicable
connotations.
“emotionally traumatic memory” IS directly equal to
a memory that causes Trauma to the person’s emotional condition.
Implicit connections to the vocabulary shall be excluded from it:
Trauma that remembered with potent emotions.
[EXCEPT]
The two items are distinct and separate without any parallel or exchangability
in meaning therefore cannot be used as synonyms.
Hkljkl;ll
The frontal to amygdalae
circuitry with right hemisphere dominance is a fundamental feature of personal
orientation in a subjective environment. Two components are pre-requisite
vocabulary:
VOCABULARY
.1 personal orientation
the person's internal, inherent manner of addressing any intake of signals from
the environment; which alternatively represents “processing” and thus must
refer to a output product even if the output is “null”; “silent”;
“passive”. The conversion of the
inherent manners for addressing signal intake to “processing” shows that
“orientation” is exchangeable with an inherent manner of address.
.2 subjective environment
the environment carries the property of subjective homogenously; the
grammatical validity of this vocabulary requires that subjective IS the nature
of the environment and thus this environment is explicitly a virtual
environment. Though environment can not be un located they can be virtual and
virtual is not synonymous to being without location. Hypermobility and
temporary duration of the feature has served to broadly incapacitate
acknowledgements of the actual definition of the vocabulary. Subjective must
refer to subject condition and environment must refer to physical isolation of
properties to Space-Time. These explicitly are Neuro Topograph; the “subject
condition” is a transformation across a definite terrain and experienced by
physical presentation to Space-Time. Despite of plasticity that encourages the
illusion of non-definiteness, it is as “non-definite” as the desert sand of the
Saharan Desert.
RECONSILIATION
Recommendation
to adopt the vocabulary “Holoform” and exclude rampant and undisciplined word
association. Holo Form.
Recommendation
to remove from vocabulary list: “subject environment” and replace all instances
with “Neuro Topograph”.
The reconciliation forces a
leaping transformation of the material intel, the statement is established:
Each person operates
responsively on the premises of Neuro Topograph inherent to them; the other
person(s) are always doing any effect whatsoever to the person via a Holo
Form.
<psyche> psychological
holo form move from the external person/environment of person = > signal
intake upon the Neuro Topograph of the person
<physic> physic holo form
move from the external person/ environment of person = >peripheral nervous
system signal / stimuli intake upon the Neuro Topograph and Physio Topographs
of the person.
Violence is a clumsy effort to
transmit a holo form. Violence works by attempting to neutralize irregularity
of a feature of the environment. If violence is enacted for the purpose of
killing, the death works to stop irregularity about that feature. All cases of
killing are representative of feature stops not person stops; hence it is only
by proxy that ever the elimination of irregularity could be claimed effective
work. Since holo form are the sole
purpose that violence inherits whatsoever, not only is the common trait about
killers to display ‘immediate need for relief’ confirmed but additionally the
complexity and mechanism of any effect whatsoever tried by living beings has
been reduced to Neuro Topographic instances where a person gets signal intake of
holo form.
“Voices in your Head” is a
fundamental concept in the scientific order of neuro topograph and holo form
communication/ transformations. “Voices in your Head” are pieces of data
retained in the neuro topographic architecture of the person which actually
sustain a big degree of incompatible surface area. Thus it is clearly not an
internally synthesized product UNLESS there is a wide stratification of
processing vectors on the neuro topograph. The comorbidity of primal intakes at
infancy with chiasm’s that stratify vectors at the neuro topograph do support
the disposition for the assuming of the incompatible surface area as holo form,
instead of as a section of the architecture on the neuro topograph. Hence;
blame others because it is not inherent: “voices in YOUR/ MY head.”
1.2.2
What is fronto amygdala circuitry and how does
it work?
Holo form intake at neuro
topograph of a person has been proved in Neuro Imaging to refer to Critical
Thinking. It is requisite to establish that Critical is a core feature of this
activation. The core component of “Critical” is extracted from signaling that
moves from the amygdala to the frontal area at predominantly the Right
Hemisphere.
Activation exhibits in the
following types of instances:
<patients tell a therapist
about a traumatic event in their past / expose their memory to the
therapist>
<therapist tries active
internal analytic to repel patient argument toward their own liability for
something; “subjective identification”>
<the Neuro Images of the
brain of the pervert fails to show activation in comparison to control
levels when holo form intake occurs; impulsive aggression ensues>
1.2.2.1
underactive fear circuits of the amygdala
Abnormal fronto-amygdala circuitry has been implicated in
impulsive aggression, a core symptom of borderline [meaningless] personality
disorder. We demonstrated a tight
coupling of metabolic activity between right OFC and ventral amygdala in
healthy subjects with dorsoventral differences in amygdala circuitry, not
present in IED-BPD. We demonstrated no significant differences in amygdala
volumes or metabolism between BPD patients and controls. FULL
http://www.nature.com/npp/journal/v32/n7/full/1301283a.html
1.2.2.2
overactive fear circuits of the amygdala
The overactive fear circuits of the amygdala have been shown
to undermine the development of the orbito-frontal systems associated with
healthy self-soothing during attachment experiences. For example, in f MRI
studies, severely neglected and traumatized Romanian orphans ( ) have “hot
amygdalas” which flare with subsequent separation and abandonment experiences.
Research also shows that the brain is capable of storing attachment traumas in
the right-brain’s sensorimotor, affective memory systems, completely split off
from the as-yet-undeveloped left-brain’s verbal reasoning processes
(Gaensbauer, 2002, p. 259; Joseph, 1982, p.243; Schore, 2003, p.74-75). These
response systems remain vigilant to possible abandonment throughout life and
produce a myriad of emotional, psychological, neuro-chemical, psycho-physiological
and behavioral deficiencies and compensatory mechanisms.
Neuro-imaging studies show that traumatic emotional memories
activate (Rauch et al., 1996), and are recalled through (Schiffer et al.,
1995), predominantly right hemisphere operations. Hippocampal damage in abused
individuals is associated with the clinical findings of impairment in affective
and memory integration (cite?).
research shows that gifted empathic therapists have greater
right frontal electrophysiological activation (Alpert et al., 1980) while they
perceive others’ emotional states.
findings suggest that exposure to graphic media images may
result in physical and psychological effects previously assumed to require
direct trauma exposure. xposure to 4 or
more hr daily of early 9/11-related television and cumulative acute stress
predicted increased incidence of health ailments 2 to 3 years later.
1.3
An Upside to Adversity?: Moderate Cumulative
Lifetime Adversity Is Associated With Resilient Responses in the Face of Controlled
Stressors
Despite common findings suggesting that lack of negative
life events should be optimal, recent work has revealed a curvilinear pattern,
such that some cumulative lifetime adversity is instead associated with optimal
well-being. This work, however, is limited in that responses to specific
stressors as they occurred were not assessed, thereby precluding investigation
of resilience. The current research addressed this critical gap by directly
testing the relationship between adversity history and resilience to stressors.
Specifically, we used a multimethod approach across two studies to assess
responses to controlled laboratory stressors (respectively requiring passive
endurance and active instrumental performance). Results revealed hypothesized
U-shaped relationships: Relative to a history of either no adversity or
nonextreme high adversity, a moderate number of adverse life events was
associated with less negative responses to pain and more positive
psychophysiological responses while taking a test. These results provide novel
evidence in support of adversity-derived propensity for resilience that
generalizes across stressors.
short term memory constraints paradigm
" new material must go in context of long term memory
to retain."
*FALSE.
material must have a setting. much of the data taken is
metacognitive and therefore impractical; delay of retainment and processing.
what is responsible for the low and poor ability for capturing essential data
from features? linguistic form significance to translate in a format viable to
output; elsewise is "emotional memory" which no one understands nor
believes in or ignores or can't realistically rely on.
author Nicholas carr book big switch on electricla industr
development and parallel to Internet dev
Nicholas continuing publications and speeches revolve the
theory that the explosion of data access on the Internet has not served
intellectual development effectively if it is overwhelming the ability to be
contained in memory; most effective if continual distractions impair short term
memory.
*MISORIENTED. the brain architecture is in such a manner
that it can use senses. If effort to acknowledge the purpose of memory and the
amplification of purposeful use of the memory one must determine what memory
should be used for. The most effective memory models are specific skill
training vectors; where all incoming data is organized around the skill
acquisition objective; because memories are retained in relative positions;
must be recalled from the location based on navigating relatively. The
environment is very broad; social settings are impractically broad; because the
decentralization of effective qualities in peer network building destablizing
data. The most effective social settings are committed peer networking. The destructuration of data is a feature of
all non-committed peer nets; the instant any/each node disconnect or move the
links in memory are fragmented; thus metacognitive capacities are transferred
the load of data effectivity retained in that broken committment on the net.
Large reliance on metacognition is a phenomenon of environments with big
amounts of failure to organize and commit. Metacognition is a secondary mode of
data; it is a supplement to navigation; it is impractical and must be transformed
into useable data at all instance for any attempt to apply. It will never be a
primary data mode.
episodic memory - an instance physically
experienced is remembered especially by virtual imagery
The medial temporal lobe memory system matures relatively
early and supports rudimentary declarative/explicit (must be said/ reiterate -
explained - semantic) memory in young infants. There is considerable
development, however, in the memory processes that underlie declarative memory
performance during infancy. Here we consider age-related changes in encoding,
retention, and retrieval in the context of current knowledge about the brain
systems that may underlie these memory processes. While changes in infants’
encoding may be attributed to rapid myelination during the first year of life,
improvements in long-term retention and flexible retrieval are likely due to
the prolonged development of the dentate gyrus. Future studies combining
measures of brain and behavior are critical in improving our understanding of
how brain development drives memory development during infancy and early
childhood.
To explain the specific pattern of impairment associated
with hippocampal amnesia, Cohen and Squire (1980) suggested that there maybe a
dissociation between remembering “that” and remembering “how”. Although the
idea that there may be more than one kind of memory was not new (Tulving,
1972)), the fact that damage to a specific area of the brain caused a specific
pattern of impairment led these researchers to suggest that different kinds of
memory might be subserved by different brain systems. It is now generally
accepted that structures in the medial temporal lobe (see Figure 1), including
the hippocampus and parahippocampal cortex, underlie the conscious recollection
of facts and events (i.e. explicit or declarative memory). In contrast, parts
of the striatum, cerebellum and brain stem are responsible for the implicit or
procedural learning that is evident in priming, conditioning, and
skill-learning tasks.
1.4
Failing to Forget
1.4.1
Inhibitory-Control Deficits Compromise Memory
Suppression in Posttraumatic Stress Disorder
Most people have experienced distressing events that they
would rather forget. Although memories of such events become less intrusive
with time for the majority of people, those with posttraumatic stress disorder
(PTSD) are afflicted by vivid, recurrent memories of their trauma. Often
triggered by reminders in the daily environment, these memories can cause
severe distress and impairment. We propose that difficulties with intrusive
memories in PTSD arise in part from a deficit in engaging inhibitory control to
suppress episodic retrieval. We tested this hypothesis by adapting the
think/no-think paradigm to investigate voluntary memory suppression of aversive
scenes cued by naturalistic reminders. Retrieval suppression was compromised
significantly in PTSD patients, compared with trauma-exposed control
participants. Furthermore, patients with the largest deficits in
suppression-induced forgetting were also those with the most severe PTSD
symptoms. These results raise the possibility that prefrontal mechanisms
supporting inhibitory control over memory are impaired in PTSD.
frontomedial temporal regions for episodic
retrieve plus hippocam complex
preferential activation - right parahippocampal
gyrus during retrive spatial location data.
right dorsolateral prefrontal cortex associated
retrive active to context data like spatial location and temporal order
1.5
Context-dependent incremental timing cells in
the primate hippocampus.
We examined timing-related signals in primate hippocampal
cells as animals performed an object-place (OP) associative learning task. We
found hippocampal cells with firing rates that incrementally increased or
decreased across the memory delay interval of the task, which we refer to as
incremental timing cells (ITCs). Three distinct categories of ITCs were
identified. Agnostic ITCs did not distinguish between different trial types.
The remaining two categories of cells signaled time and trial context together:
One category of cells tracked time depending on the behavioral action required
for a correct response (i.e., early vs. late release), whereas the other
category of cells tracked time only for those trials cued with a specific OP
combination. The context-sensitive ITCs were observed more often during
sessions where behavioral learning was observed and exhibited reduced
incremental firing on incorrect trials. Thus, single primate hippocampal cells
signal information about trial timing, which can be linked with trial
type/context in a learning-dependent manner.
1.6
S. Ciocchi et al., “Selective information
routing by ventral hippocampal CA1 projection neurons,” Science, 348:560-63,
2015.
While the rats freely explored an open environment, their
hippocampi sent information to all three targets. However, during goal-directed
behavior, in which the rats received a reward for navigating to a particular
zone, certain hippocampal neurons projecting to the nucleus accumbens and
prefrontal cortex were activated, while a subset of neurons projecting to the
nucleus accumbens were inhibited. Lastly, during a task that made the rats
anxious, hippocampal neurons that specifically targeted the prefrontal cortex
alone were activated.
1.7
V. Leone et al., “Effects of diurnal variation
of gut microbes and high-fat feeding on host circadian clock function and
metabolism,” Cell Host & Microbe, doi:10.1016/j.chom.2015.03.006, 2015.
1.8
Explain others by attributing their unobservable
mind
People typically explain others’ behaviors by attributing
them to the beliefs and motives of an unobservable mind. Although such
attributional inferences are critical for understanding the social world, it is
unclear whether they rely on processes distinct from those used to understand
the nonsocial world. In the present study, we used functional MRI to identify
brain regions associated with making attributions about social and nonsocial
situations. Attributions in both domains activated a common set of brain
regions, and individual differences in the domain-specific recruitment of one
of these regions—the dorsomedial prefrontal cortex (DMPFC)—correlated with
attributional accuracy in each domain. Overall, however, the DMPFC showed
greater activation for attributions about social than about nonsocial
situations, and this selective response to the social domain was greatest in
participants who reported the highest levels of social expertise. We conclude
that folk explanations of behavior are an expert use of a domain-general cognitive
ability.
1.9
Heart Rate Variability Predicts Control Over
Memory Retrieval
Stopping retrieval of unwanted memories has been
characterized as a process that requires inhibition. However, little research
has examined the relationship between control over memory retrieval and
individual differences in inhibitory control. Higher levels of resting heart
rate variability (HRV) are associated with greater inhibitory control, as
indicated by better performance on a number of cognitive, affective, and motor tasks.
Therefore, we tested the hypothesis that higher levels of resting HRV predict
enhanced memory inhibition as indexed by performance on the think/no-think
task. Efforts to suppress no-think word pairs resulted in impaired recall for
those items, as in past studies. Moreover, higher levels of resting HRV were
associated with more successful suppression, as indicated by lower recall of
the to-be-avoided stimuli relative to baseline stimuli. These findings are
among the first to suggest that physiological markers of inhibitory control can
be used to index a person’s capacity to control unwanted memories.
1.10Greater Maternal
Insensitivity in Childhood Predicts Greater Electrodermal Reactivity During
Conflict Discussions With Romantic Partners in Adulthood
In this study, we drew on prospective, longitudinal data to
investigate the long-term predictive significance of the quality of early
parent-child relationship experiences for adults’ sympathetic nervous system
(SNS) activity during conflict discussions with their romantic partners.
Maternal sensitivity was repeatedly assessed across childhood via direct
observations of mother-child interactions. When the children in the study
became adults (34–37 years old), electrodermal activity—an index of SNS arousal
and a psychophysiological marker of behavioral inhibition—was recorded for 37
participants while at rest and while they attempted to resolve conflicts in
their romantic relationships. Individuals who had experienced less sensitive
maternal caregiving during childhood had greater increases in electrodermal
activity during conflict discussions with their adult partners, relative to
resting conditions. This longitudinal association was not accounted for by
observed or self-reported romantic-relationship quality, gender, ethnicity, or
early socioeconomic factors.
1.11Dual-Hormone Changes Are
Related to Bargaining Performance
In the present research, we found that endogenous
testosterone and cortisol changes were jointly related to bargaining outcomes.
In a face-to-face competitive negotiation (Study 1) and a laboratory-based
bargaining game (Study 2), testosterone rises were associated with high
earnings and high relationship quality, but only if cortisol dropped. If
cortisol rose, testosterone rises were associated with low earnings and poor
relationship quality. Conflict between financial and social goals was related
to the financially costly dual-hormone profile (testosterone increase and
cortisol decrease), whereas the absence of such conflict was related to the financially
adaptive dual-hormone profile (testosterone increase and cortisol increase).
The findings suggest that when cortisol decreases, rising testosterone is
implicated in adaptive bargaining behavior that maximizes earnings and
relationship quality. But when cortisol increases, rising testosterone is
related to conflict between social and financial motives, weak earnings, and
poor relationship quality. These results imply that there are both bright and
dark sides to rising testosterone in economic social interactions that depend
on fluctuations in cortisol.
1.12Looking Inward: Shifting
Attention Within Working Memory Representations Alters Emotional Responses
to focusing on an arousing portion of a negative-image
representation within WM, focusing on a neutral portion of the representation
reduced both self-reported negative emotion and the late positive potential, a
robust neural measure of emotional reactivity. These data suggest that
selective attention can alter emotional responses arising from affective
representations active within WM.
1.13rediscovery &
time-inconsistent choices:
underestimating the pleasure of rediscovery leads to
time-inconsistent choices: Individuals forgo opportunities to document the
present but then prefer rediscovering those moments in the future to engaging
in an alternative fun activity. Underestimating the value of rediscovery is
linked to people’s erroneous faith in their memory of everyday events. By
documenting the present, people provide themselves with the opportunity to rediscover
mundane moments that may otherwise have been forgotten.
1.14Conduct problems
Conduct problems represent a major societal problem and
include physical aggression, cruelty to others, and a lack of empathy, or
"callousness." In the United Kingdom, where the study was conducted,
about 5 percent of children qualify for a diagnosis of conduct problems. But
very little is known about the underlying biology. In the new study, Dr. Viding, Patricia
Lockwood and their colleagues scanned children's brains by functional magnetic
resonance imaging (fMRI) to see how those with conduct problems differ in their
response to viewing images of others in pain.
The brain images showed that, relative to controls, children with conduct
problems show reduced responses to others' pain specifically in regions of the
brain known to play a role in empathy. The researchers also saw variation among
those with conduct problems, with those deemed to be more callous showing lower
brain activation than less callous individuals.
Highlights
•Children with conduct problems showed reduced neural
responses to others’ pain
•Reductions in anterior insula, anterior cingulate cortex,
and inferior frontal gyrus
•Callous traits associated with the magnitude of reduction
•Findings may reflect early neurobiological risk for adult
psychopathy
Summary
Children with conduct problems (CP) persistently violate
others’ rights and represent a considerable societal cost [ 1 ]. These children
also display atypical empathic responses to others’ distress [ 2 ], which may
partly account for their violent and antisocial behavior. Callous traits index
lack of empathy in these children and confer risk for adult psychopathy [ 3 ].
Investigating neural responses to others’ pain is an ecologically valid method
to probe empathic processing [ 4 ], but studies in children with CP have been
inconclusive [ 5, 6 ]. Using functional magnetic resonance imaging (fMRI), we
measured neural responses to pictures of others in pain (versus no pain) in a
large sample of children with CP and matched controls. Relative to controls,
children with CP showed reduced blood oxygen level-dependent responses to
others’ pain in bilateral anterior insula (AI), anterior cingulate cortex
(ACC), and inferior frontal gyrus, regions associated with empathy for pain in
previous studies [ 7, 8 ]. In the CP group, callous traits were negatively
associated with responses to others’ pain in AI and ACC. We conclude that
children with CP have atypical neural responses to others’ pain. The negative
association between callous traits and AI/ACC response could reflect an early
neurobiological marker indexing risk for empathic deficits seen in adult
psychopathy.
Holo Form OR Neuro Topograph
2 Holo
Form OR Neuro Topograph
2.1
Un sorted
nonverbal “implicit relational knowledge” (Stern,
Brucshweiler-Stern et al., 1998; in Schore, 2003, p. 53)
Allan Schore (2003), it has been demonstrated that it is
built into our DNA such that primary caregivers act as psychobiological
regulators of hormones that directly affect gene transcription.
efforts to establish
human relatedness that is required for emotional and dendritic growth
fearful, depressed or
sleep-deprived brain cannot engage, connect, or sprout new learning circuits
severe and enduring disruption of serotonin, dopamine, and
opioid systems. This leads to further affective disorganization then
dissociative somnolence
intrinsic abnormality of sexual development
obessive
compulsive
impulse control
fantasy
urges
2.2
Mindsets of Mass Destruction
library of congress - federal research division the
sociology and psychology of terrorism.
[b.j. berkowitz 1972] 6 psychological types that have the
tendency to threaten use of weapons of mass destruction: paranoids; paranoid
schizophrenics; borderline mental defectives; schizophrenic types; passive
aggressive personality; sociopath <highest indication>
> suggestion: terrorist want a lot of people watching not
a lot of people dead.
2.3
Mitochondrial Gene Expression Profiles and
Metabolic Pathways in the Amygdala Associated with Exaggerated Fear in an
Animal Model of PTSD.
The metabolic mechanisms underlying the development of
exaggerated fear in post-traumatic stress disorder (PTSD) are not well defined.
In the present study, alteration in the expression of genes associated with
mitochondrial function in the amygdala of an animal model of PTSD was
determined. Amygdala tissue samples were excised from 10 non-stressed control
rats and 10 stressed rats, 14 days
post-stress treatment. Total RNA was isolated, cDNA was synthesized, and gene
expression levels were determined using a cDNA microarray. During the
development of the exaggerated fear associated with PTSD, 48 genes were found
to be significantly upregulated and 37 were significantly downregulated in the
amygdala complex based on stringent criteria (p < 0.01). Ingenuity pathway
analysis revealed up- or downregulation in the amygdala complex of four
signaling networks - one associated with inflammatory and apoptotic pathways,
one with immune mediators and metabolism, one with transcriptional factors, and
one with chromatin remodeling. Thus, informatics of a neuronal gene array
allowed us to determine the expression profile of mitochondrial genes in the
amygdala complex of an animal model of PTSD. The result is a further understanding
of the metabolic and neuronal signaling mechanisms associated with delayed and
exaggerated fear. FULL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172054/
Pain
3 PAIN
life is tough, people are cruel,
and others are grossly ungrateful or bad, its very unfair. and the reason for
idolizing navy seals and heros has a lot to do with acknowledging how they
suffered day in and day out, feeling pain and fear and discomfort and stress.
especially navy seals and heros, because they symbolize how it was SO HARD that
only 10 PERCENT made it through. and that's just how hard it really is.
how the experience had permanence.
and the loss was loss of things irreplaceable, in a way from their experience
of life they can never get back. to the other side of death they had to suffer
that loss and no justice was given.
3.1
The induction of pain: an integrative review.
The highly disagreeable sensation of pain results from an
extraordinarily complex and interactive series of mechanisms integrated at all
levels of the neuroaxis, from the periphery, via the dorsal horn to higher
cerebral structures. Pain is usually elicited by the activation of specific
nociceptors ('nociceptive pain'). However, it may also result from injury to
sensory fibres, or from damage to the CNS itself ('neuropathic pain'). Although
acute and subchronic, nociceptive pain fulfils a warning role, chronic and/or
severe nociceptive and neuropathic pain is maladaptive. Recent years have seen
a progressive unravelling of the neuroanatomical circuits and cellular
mechanisms underlying the induction of pain. In addition to familiar
inflammatory mediators, such as prostaglandins and bradykinin,
potentially-important, pronociceptive roles have been proposed for a variety of
'exotic' species, including protons, ATP, cytokines, neurotrophins (growth
factors) and nitric oxide. Further, both in the periphery and in the CNS,
non-neuronal glial and immunecompetent cells have been shown to play a
modulatory role in the response to inflammation and injury, and in processes
modifying nociception. In the dorsal horn of the spinal cord, wherein the
primary processing of nociceptive information occurs, N-methyl-D-aspartate
receptors are activated by glutamate released from nocisponsive afferent
fibres. Their activation plays a key role in the induction of neuronal
sensitization, a process underlying prolonged painful states. In addition, upon
peripheral nerve injury, a reduction of inhibitory interneurone tone in the
dorsal horn exacerbates sensitized states and further enhance nociception. As
concerns the transfer of nociceptive information to the brain, several pathways
other than the classical spinothalamic tract are of importance: for example,
the postsynaptic dorsal column pathway. In discussing the roles of supraspinal
structures in pain sensation, differences between its 'discriminative-sensory'
and 'affective-cognitive' dimensions should be emphasized. The purpose of the
present article is to provide a global account of mechanisms involved in the
induction of pain. Particular attention is focused on cellular aspects and on
the consequences of peripheral nerve injury. In the first part of the review,
neuronal pathways for the transmission of nociceptive information from
peripheral nerve terminals to the dorsal horn, and therefrom to higher centres,
are outlined. This neuronal framework is then exploited for a consideration of
peripheral, spinal and supraspinal mechanisms involved in the induction of pain
by stimulation of peripheral nociceptors, by peripheral nerve injury and by
damage to the CNS itself. Finally, a hypothesis is forwarded that neurotrophins
may play an important role in central, adaptive mechanisms modulating
nociception. An improved understanding of the origins of pain should facilitate
the development of novel strategies for its more effective treatment.
3.2
An overview of pain pathways is presented,
beginning in the periphery and progressing centrally, and
the ascending and descending pathways are described in detail. RESULTS:
The nociceptive pathway, consisting of the classic three-neuron chain,
is now understood to be a dual system at each level, and the sensation of pain
is thought to arrive in the central nervous system with the discriminative
component of pain ("first pain") carried separately from the
affective-motivational component of pain ("second pain"). In addition
to spinal control mechanisms of nociceptive transmission, descending pathways
that originate in three major areas--the cortex, thalamus, and brain stem--can
modify functions at the spinal level. At every level of the nervous system, a
close relationship prevails between somatic pain pathways and visceral
pathways. This relationship likely accounts for the transmission of visceral
pain and also for autonomic responses to somatic pain and somatic responses to
visceral pain.
3.3
Peripheral nociceptive messages
Peripheral
nociceptive messages are conveyed by a mosaic of unmyelinated free fibres
distributed throughout cutaneous, muscular and articular tissue, and within the
visceral walls. They are then transmitted via various nerve endings (polymodal
nociceptors) by small diameter A delta and C fibres, which are activated by
mechanical, thermal and chemical stimuli. It is nevertheless difficult to
ascertain whether these small diameter fibres are involved only in nociception
(specific nociceptors) or whether pain causes an excessive activation of these
receptors, which under normal conditions have a role in the reflex that
regulates various functions (nonspecific nociceptors). Numerous chemical
substances play a part in generating nociceptive impulses (e.g. histamine,
serotonin, prostaglandins). Furthermore, the role of neuropeptides, such as
calcitonin gene-related peptide and particularly substance P, has been clearly
demonstrated in the activation of early neurogenic inflammation. Other
substances, such as bradykinin and cytokines, are involved in prolonging the
sensation of pain. Nerve growth factor also prolongs the sensation of pain by
increasing the cellular excitability of nociceptors and promoting the action of
the sympathetic nervous system, which has a major role in controlling pain. The
very great diversity of all these interacting substances makes the
pharmacological treatment of pain extremely complex. Nevertheless, new therapeutic
advances are providing interesting approaches, particularly the development of
specific inhibitors of cyclo-oxygenase 2 (COX 2), which is produced by the
inflammatory process. Such inhibitors would preserve COX 1, which is both
constitutive and physiological, and thereby provide improved tolerability
compared with currently used NSAIDs, which act upon both COX pathways. A major
focus of research relating to new analgesics is the development of synthetic
antagonists of bradykinin, substance P and N-methyl-D-aspartate receptors. An
improved understanding of anatomical and electrophysiological processes has led
to the discovery of new ascending pathways that transmit nociceptive messages
to the reticular formation, the hypothalamus, and the amygdala, as well as to
certain areas of the cortex. As a result the notion of one single pain centre
is no longer valid. This idea is further reinforced by the knowledge that, at
different stages of the pain pathway, different control systems constantly
modulate the transmission of nociceptive information. Consequently, at a spinal
level, activation of the large diameter cutaneous fibres (A alpha et beta)
blocks pain stimuli transmitted by the small diameter fibres. Knowledge of this
"gate control' mechanism of the posterior horn of the spinal cord is put
to practical application in treatments involving transcutaneous electrical
nerve stimulation.
3.4
Brain habituation during repeated exposure to
fearful and neutral faces: a functional MRI study.
Central nervous system habituation in humans was studied
using functional magnetic resonance imaging and repeated presentations of
single fearful and neutral faces. Habituation of
blood-oxygenation-level-dependent (BOLD) signal during exposure to face
stimuli, collapsed over fearful and neutral expressions, was evident in the
right amygdala and hippocampus, as well as in the medial/inferior temporal
cortex bilaterally. In the hippocampus, significantly greater habituation was
evident on the right as compared to the left side, which could reflect the
visual nature of the stimuli. There were no time by expression interaction
effects in these regions, suggesting similar neural attenuation rates to
fearful and neutral face stimuli. These results indicate that brain regions
involved in novelty detection and memory processing habituate at similar rates
regardless of whether the face in focus displays an aversive emotional
expression or not.
3.5
Activation of the prefrontal cortex during
judgments of recency: a functional MRI study.
Animal and human lesion studies have consistently shown that
damage to the prefrontal lobe disrupts performance on tasks requiring memory
for temporal context. In this study, functional magnetic resonance imaging
(fMRI) was used to explore the brain regions associated with judgements of
relative recency in healthy humans. Bilateral dorsolateral prefrontal cortex
(Brodmann's area [BA] 9) was more active during a verbal recency judgment task
than during a non-mnemonic control task. Activation related to temporal context
recognition was also observed in midline supplementary motor area (BA 6) and
left precuneus (BA 7). This study provides further evidence that memory for
temporal context requires the prefrontal cortex and is the first to demonstrate
this association in healthy humans. The current findings also suggest the
possibility that recognition of context and recognition of episodic content may
involve similar brain systems.
3.6
Pain is subjective
Pain, while salient, is highly subjective. A sensation
perceived as painful by one person may be perceived as uncomfortable, not
painful or even pleasant to others. Within the same person, pain may also be
modulated according to its threat value and the context in which it is
presented. Imaging techniques, such as functional magnetic resonance imaging
and positron emission tomography, have identified a distributed network in the
brain, the pain-relevant brain regions, that encode the sensory-discriminative
aspect of pain, as well as its cognitive and affective/emotional factors.
Current knowledge also implicates the prefrontal cortex as the modulatory area
for pain, with its subdivisions forming the cortico-cortical pathway, an
alternative pain modulatory pathway distinct from the descending modulatory
pathway of pain. These findings from neuroimaging in human subjects have paved
the way for the molecular mechanisms of pain modulation to be explored in
animal studies.
3.7
Pain pathways in the primate.
From the work reviewed here, it appears that the classical
view that there is a sensory channel for pain sensation rather like sensory
channels for other sensations seems plausible. However, pain has the property
of producing more prominent motivational-affective behaviors than do other
sensations (although there are certainly motivational-affective components of
the responses to many sensory experiences, such as a verbal attack or the odor
of a favorite perfume). It may be that certain nociceptive neurons, such as the
STT cells that project to the medial thalamus that have total body receptive
fields and many similar spinoreticular neurons, are concerned not so much with
sensory events but rather with motivational-affective responses. Nevertheless,
there are specific nociceptive afferent fibers, nociceptive spinothalamic tract
cells with restricted receptive fields, nociceptive VPL thalamic and SI
cortical neurons that presumably could play a crucial role in the
sensory-discriminative aspects of pain (signalling, for example, stimulus
intensity, location, duration, rate, and quality). Interestingly, many
nociceptive neurons receive a convergent input from both sensitive
mechanoreceptors and from nociceptors and so can be classified as "wide
dynamic range" or multiconvergent neurons. It is not at all clear what the
significance is of this kind of multimodal convergence. One possibility is that
the weaker tactile input is treated as noise and largely ignored by higher
processing centers in the brain. Another possibility is that WDR cells are
switched in function by the action of descending pathways originating in the
brain stem or cerebral cortex (cf., Gerhart et al., 1984; Yezierski et al.,
1983). In any event, the solution of this problem is likely to be very
important for the full understanding of the coding properties of nociceptive neurons,
and this issue is reminiscent of the coding problem discussed by David Smith in
this volume with respect to the gustatory system.
3.8
Nociceptive pathways: anatomy and physiology of
nociceptive ascending pathways.
In primates, the principal nociceptive pathways ascend in
the anterolateral quadrant of the spinal cord. Among these, the spinothalamic
tract (s.t.t.) is the best studied. Cells in Rexed's laminae I and V project to
the ventro-posterolateral (v.p.l.) thalamic nucleus. Other cells in the same and
deeper laminae terminate in the intralaminar complex. Spinothalamic tract cells
may be nociceptive-specific or multireceptive. Those ending in v.p.l. have
restricted, contralateral receptive fields, whereas those projecting to the
intralaminar region often have large, bilateral receptive fields.
Spinoreticular tract (s.r.t.) cells are concentrated in laminae VII and VIII
and may be nociceptive. It is proposed that the s.t.t. contributes to
sensory-discriminative processing of pain and that the s.t.t. and s.r.t. play a
role in the motivational-affective components of pain. Alternative nociceptive
pathways are the spinocervical and postsynaptic dorsal column tracts.
3.9
Plasticity of nociception: recent advances in
function-oriented structural pain research.
Traditional concept holds that the pain unit consists of
three neurons. The first of these, the primary nociceptive neuron, starts with
the nociceptors and terminates in the dorsal spinal cord. The second one,
called spinothalamic neuron, crosses over in front of the central canal and
connects the dorsal horn with the thalamus. The third one, called
thalamo-cortical neuron, terminates in the "pain centres" of the
cerebral cortex. While this simplistic scheme is useful for didactic purposes,
the actual situation is more complex. First, in the periphery it is only
nociception that occurs, while pain is restricted to the levels of thalamus and
the cortex. Second, pain results from interactions of excitation and
inhibition, from divergence and convergence and from attention and distraction,
in a diffuse and plastic system, characteristic for all levels of organization.
This study describes the major cytochemical markers of primary nociceptive
neurons followed by the presentation of recent data on the functional anatomy
of nociception and pain, with special focus on the intrinsic antinociceptive
system and the role of nitrogen oxide, opiate receptors, nociceptin and
nocistatin. In addition to the classic intrinsic antinociceptive centres such
as the periaqueductal gray matter and the raphe nuclei, roles of several
recently discovered members of the antinociceptive system are discussed, such
as the pretectal nucleus, the reticular formation, the nucleus accumbens, the
nucleus tractus solitarii, the amygdala and the reticular thalamic nucleus,
this latter being a coincidence detector and a centre for attention and
distraction. The localisation of cortical centres involved in the generation of
pain are presented based on the results of studies using imaging techniques, and
the structural basis of corticospinal modulation is also outlined. Seven levels
of nociception and pain are highlighted where pharmacological intervention may
be successful, 1. the peripheral nociceptor, 2. the spinal ganglion, 3. the
multisynaptic system of the dorsal horn, 4. the modulatory system of the brain
stem, 5. the antinociceptive system, 6. the multisynaptic system of the
thalamus, and 7. the cortical evaluating and localisation system that is also
responsible for descending (inhibiting) control. The many levels of nociception
and pain opens new ways both for pharmacological research and the general
practitioner aiming to alleviate pain.
3.10Alleviation of neuropathic
pain by regulating T-type calcium channels in rat anterior cingulate cortex
It has been demonstrated that administration of T-type
calcium channel (TCC) inhibitors could relieve the neuropathic pain by
intraperitoneally or intrathecally. TCCs are not only expressed in dorsal root
ganglia or dorsal horn, but also in some of the pain associated brain regions.
In the present study, we sought to investigate whether modulating TCCs in the
anterior cingulate cortex (ACC) could alleviate the neuropathic pain.
Results
(1) Cav3.2 was up regulated in rat ACC after chronic
constriction injury (CCI). (2) T-type calcium current intensity was increased
in CCI animal model. (3) TCC inhibitor reduced miniature excitatory
postsynaptic currents frequency of ACC neurons in CCI animal model. (4) TCC
inhibitor suppressed the firing rate of ACC neurons in CCI animal model. (5)
Both mechanical and thermal allodynia were partially relieved by ACC
microinjection with TCC inhibitor.
3.11Reward skewness coding in
the insula independent of probability and loss
Rewards in the natural environment are rarely predicted with
complete certainty. Uncertainty relating to future rewards has typically been
defined as the variance of the potential outcomes. However, the asymmetry of
predicted reward distributions, known as skewness, constitutes a distinct but
neuroscientifically underexplored risk term that may also have an impact on
preference. By changing only reward magnitudes, we study skewness processing in
equiprobable ternary lotteries involving only gains and constant probabilities,
thus excluding probability distortion or loss aversion as mechanisms for
skewness preference formation. We show that individual preferences are
sensitive to not only the mean and variance but also to the skewness of
predicted reward distributions. Using neuroimaging, we show that the insula, a
structure previously implicated in the processing of reward-related
uncertainty, responds to the skewness of predicted reward distributions. Some
insula responses increased in a monotonic fashion with skewness (irrespective
of individual skewness preferences), whereas others were similarly elevated to
both negative and positive as opposed to no reward skew. These data support the
notion that the asymmetry of reward distributions is processed in the brain
and, taken together with replicated findings of mean coding in the striatum and
variance coding in the cingulate, suggest that the brain codes distinct aspects
of reward distributions in a distributed fashion.
3.12Neuronal Mechanisms of
Repetition Priming in Occipitotemporal Cortex: Spatiotemporal Evidence from
Functional Magnetic Resonance Imaging and Electroencephalography
FULL TEXT http://www.jneurosci.org/content/25/13/3414.long
Repeated stimulus presentation (priming) is generally
associated with a reduction in neuronal firing, macroscopically mirrored by a
decrease in oscillatory electrophysiological markers as well as reduced
hemodynamic responses. However, these repetition effects seem to be dependent
on stimulus familiarity. We investigate the spatiotemporal correlates of
repetition priming in cortical word-recognition networks and their modulation
by stimulus familiarity (i.e., words vs pseudowords). Event-related functional
magnetic resonance imaging results show reduced activation for repeated words
in occipitotemporal cortical regions. Electroencephalogram recordings reveal a
significant reduction of induced gamma-band responses (GBRs) between 200 and
350 ms after stimulus onset, accompanied by a decrease in phase synchrony
between electrode positions. Pseudoword repetition, in contrast, leads to an activation
increase in the same areas, to increased GBRs, and to an increased phase
coupling. This spatiotemporal repetition by stimulus type interaction suggests
that qualitatively distinct mechanisms are recruited during repetition priming
of familiar and unfamiliar stimuli. Repetition of familiar stimuli leads to a
“sharpening” of extrastriate object representations, whereas the repetition of
unfamiliar stimuli results in the “formation” of a novel cortical network by
means of synchronized oscillatory activity. In addition to isolating these
mechanisms, the present study provides the first evidence for a possible link
between induced electrophysiological and hemodynamic measures of brain
activity. Introduction
Repeated processing of identical stimuli (behaviorally
mirrored in repetition priming effects) is associated with a decrease in the
strength of stimulus-related neuronal responses, a phenomenon known as
repetition suppression (Schacter and Buckner, 1998). Wiggs and Martin (1998),
elaborating on the ideas of Desimone (1996), suggested that repetition
suppression is a by-product of a “sharpening” process of cortical object
representations. In this view, neurons that code features not essential for
processing a repeated stimulus drop out of the cell assembly coding this
object, thus yielding a more efficient neuronal stimulus representation.
Recent functional neuroimaging research in humans has
demonstrated that repetition suppression occurs in response to familiar, but
not unfamiliar, stimuli. Repetition of unfamiliar faces and symbols causes an
activation increase in brain areas such as the right fusiform gyrus (R. Henson
et al., 2000; Thiel et al., 2002). Because this stimulus
familiarity-by-repetition interaction is difficult to reconcile with classical
theories of repetition priming, R. Henson et al. (2000) suggested that
repetition-related increases might reflect the formation of new memory traces
for previously unfamiliar items.
3.13Greater externalizing
personality traits predict less error-related insula and anterior cingulate
cortex activity in acutely abstinent cigarette smokers
Externalizing is a broad personality construct characterized
by deficient impulse control, vulnerability to addiction and reduced
neurobiological indices of error processing. The insula and dorsal anterior
cingulate cortex (dACC) are regions critically linked with error processing as
well as the perpetuation of cigarette smoking. As such, we examined the
interrelations between externalizing tendencies, erroneous task performance,
and error-related insula and dACC activity in overnight-deprived smokers
(n = 24) and non-smokers (n = 20).
Suggesting a neurobiological contribution to such suboptimal performance
among smokers, higher externalizing also predicted less recruitment of the
right insula and dACC following error commission. Critically, this
error-related activity fully mediated the relationship between externalizing
traits and error rates. That is, higher externalizing scores predicted less
error-related right insula and dACC activity and, in turn, less error-related
activity predicted more errors. Relating such regional activity with a
clinically relevant construct, less error-related right insula and dACC
responses correlated with higher tobacco craving during abstinence. Given that
inadequate error-related neuronal responses may contribute to continued drug
use despite negative consequences, these results suggest that externalizing
tendencies and/or compromised error processing among subsets of smokers may be
relevant factors for smoking cessation success.
3.14Fibromyalgia
The pain in Fibromyalgia (FM) is difficult to treat and
functional mobility seems to be an important comorbidity in these patients that
could evolve into a disability. In this study we wanted to investigate the
analgesic effects of music in FM pain. Twenty-two FM patients were passively
exposed to (1) self-chosen, relaxing, pleasant music, and to (2) a control
auditory condition (pink noise). They rated pain and performed the “timed-up
& go task (TUG)” to measure functional mobility after each auditory
condition. Listening to relaxing, pleasant, self-chosen music reduced pain and
increased functional mobility significantly in our FM patients. The
music-induced analgesia was significantly correlated with the TUG scores;
thereby suggesting that the reduction in pain unpleasantness increased
functional mobility. Notably, this mobility improvement was obtained with music
played prior to the motor task (not during), therefore the effect cannot be
explained merely by motor entrainment to a fast rhythm. Cognitive and emotional
mechanisms seem to be central to music-induced analgesia. Our findings
encourage the use of music as a treatment adjuvant to reduce chronic pain in FM
and increase functional mobility thereby reducing the risk of disability.
Pain is a protective perceptual response shaped by
contextual, psychological, and sensory inputs that suggest danger to the body.
Sensory cues suggesting that a body part is moving toward a painful position
may credibly signal the threat and thereby modulate pain. In this experiment,
we used virtual reality to investigate whether manipulating visual
proprioceptive cues could alter movement-evoked pain in 24 people with neck
pain. We hypothesized that pain would occur at a lesser degree of head rotation
when visual feedback overstated true rotation and at a greater degree of
rotation when visual feedback understated true rotation. Our hypothesis was
clearly supported: When vision overstated the amount of rotation, pain occurred
at 7% less rotation than under conditions of accurate visual feedback, and when
vision understated rotation, pain occurred at 6% greater rotation than under
conditions of accurate visual feedback. We concluded that visual-proprioceptive
information modulated the threshold for movement-evoked pain, which suggests
that stimuli that become associated with pain can themselves trigger pain.
Understanding exactly how the hippocampus sorts and packages
information to be sent to the correct targets is the “next big question,” said
psychologist Michael Fanselow of the University of California, Los Angeles, who
was not involved in the work. For now, though, the results could spur
translational research into disorders such as anxiety or post-traumatic stress
disorder. A problem with many psychoactive drugs is that they “affect the whole
brain” and create “a lot of desired and a lot of undesirable effects combined,”
Fanselow said. These latest results in rats suggest that, in the future, “we
may be able to help those conditions by targeting specific groups of cells
within the hippocampus,” he added.
3.15Amygdala ß-noradrenergic
receptors modulate delayed downregulation of dopamine activity following
restraint.
Stress, which involves a heightened arousal and excitability,
triggers important adaptive responses to maintain homeostasis and prepare a
response. In the current studies, we administered a psychological stressor of 2
h acute restraint on rats, and found that 24 h after the cessation of the
restraint session, there was a significant decrease in ventral tegmental area
dopaminergic (DA) neuron population activity and a significant attenuation in
amphetamine-induced locomotor activity. Systemic or intra-basolateral nuclei of
the amygdala administration of the ß-noradrenergic receptor antagonist,
propranolol, reversed the decrease, suggesting that the delayed attenuation of
DA neuron firing following a stressor depends on a noradrenaline-mediated
mechanism. This alteration in DA activity may adaptively prepare the individual
to avoid the stressor, or in the extreme, may be a factor that contributes to
pathological changes in behavior or physiological responses.
3.16Corticotropin (ACTH) acts
directly on amygdala neurons to down-regulate corticotropin-releasing hormone
gene expression.
The hormone corticotropin (ACTH) is employed as therapy for
diverse neurological disorders, but the mechanisms for its efficacy remain
unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and
most ACTH effects on the central nervous system (CNS) have been attributed to
activation of glucocorticoid receptors. However, in several human disorders,
ACTH has therapeutic actions that differ qualitatively or quantitatively from
those of steroids. This study tested the hypothesis that ACTH directly
influences limbic neurons via the recently characterized melanocortin receptors
and focused on the effects of ACTH on the expression of corticotropin-releasing
hormone (CRH), a neuropeptide involved in neuroimmune functions and in certain
developmental seizures. The results demonstrated that ACTH potently reduced CRH
expression in amygdala neurons. This down-regulation was not abolished by
experimental elimination of steroids or by blocking their receptors and was
reproduced by a centrally administered ACTH fragment that does not promote
steroid release. Importantly, selective blocking of melanocortin receptors
prevented ACTH-induced down-regulation of CRH expression. Taken together, these
data indicate that ACTH activates central melanocortin receptors to modulate
CRH gene expression in amygdala, supporting the notion that direct,
steroid-independent actions of ACTH may account for some of its established
clinical effects on the CNS.
