Neuro Chapter 18: Limbic system: Homeostasis, Olfaction, Memory, and Emotion (p. 838-858)
Jobs of the limbic system:
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Olfaction – done by the olfactory cortex
Memory – done by the hippocampal formation
Emotions and drives – done by the amygdala
Homeostasis through autonomics and neuroendocrine control – done by the hypothalamus
People with medically refractory temporal lobe epilepsy can be treated by removing that temporal lobe
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Never do bilateral, because it causes memory loss where they can’t remember new experiences
that happen to them after the surgery
Declarative (aka explicit) memory – conscious recollection of facts or experiences
Nondeclarative (aka implicit) memory – nonconscious learning of skills, habits, and other acquired
behaviors
Amnesia – declarative memory loss (so can’t recall facts or experiences)
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Amnesia is typical of bilateral medial temporal lobe or bilateral medial diencephalic lesions
Unilateral lesions don’t cause severe memory loss, but unilateral lesions of the dominant
(usually left) medial temporal or diencephalic area can cause some problems with verbal
memory, and unilateral lesions of the nondominant (usually right) hemisphere can cause
problems in visual-spatial memory
Unlike declarative memory, specific lesions don’t usually cause clinically significant selective loss of
nondeclarative memory
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Learning of skills and habits involves plasticity in several areas, including the basal ganglia,
cerebellum, and motor cortex
The caudate nucleus is important in habit learning, and problems here can cause obsessivecompulsive disorder
Processes in converting short-term memory to long-term for declarative memory:
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Seconds-to-minutes – involve electrical activity in neurons, with changes in intracellular calcium
and other second messengers
o Less than a second – called “attention” or “registration”
 Happens in the brainstem/diencephalon activating system, frontoparietal
association networks, and in the cortex
o Seconds to minutes – called “working memory”
 Happens in the frontal association cortex and other parts of the cortex
Minutes-to-hours – involves protein phosphorylation and expression of immediate early genes
o Minutes to years – called “consolidation”
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 Happens in medial temporal area, medial diencephalon, and parts of the cortex
Hours-to-years – gene transcription and translation is modified more to cause structural
changes of proteins and neurons
o Years – done by the cortex
When testing memory of a patient, you test immediate recall, attention, and working memory, by
asking them to repeat back to you lists of #’s or words forward and backward
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These need to be working right in order to successfully encode in declarative memory
These actions don’t depend on the medial temporal or medial diencephalic memory system
Alertness and attention are mediated by an interaction of brainstem-diencephalic and
frontoparietal networks, acting on specific areas of cortex involved in holding a concept in
conscious awareness
Working memory involves holding a concept briefly in awareness while doing something
mentally (ex: doing math)
o Working memory needs the dorsolateral prefrontal association cortex to be involved
Once you’ve tested attention and confirmed their ability to register new info, test recent memory by
giving them several words to remember and then testing for recall of the words 4-5 minutes later
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Recent memory is impaired in problems of the bilateral medial temporal or medial
diencephalic areas
Then check remote memory by asking them about personal info like their address or who’s president
People with bilateral medial temporal or medial diencephalic lesions can’t recall facts or events for more
than a few minutes
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So medial temporal and diencephalic structures mediate a process where declarative memories
are gradually consolidated in the neocortex
Through this process, declarative memories can be recalled through activity in the neocortex,
without any involvement by the medial temporal or medial diencephalic areas
Anterograde amnesia – problem forming new memories, from the time of their brain injury onward
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Ex: after the injury, you can’t learn your address and when asked tell them your address when
you were a kid
Retrograde amnesia – loss of memories from a period of time before the brain injury
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Ex: after the injury, you can remember childhood, but not a the couple of years before the
injury
Medial temporal lobe and medial diencephalic memory system lesions often show a combo of
anterograde and retrograde amnesia
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Retrograde amnesia suggests that recent memories, for a period of up to several years, depend
on the normal working of medial temporal and diencepahlic areas, while more remote
memories do not
Retrograde amnesia is graded, with the memories from the time just before the injury being the most
severely impaired
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In people with reversible causes of retrograde amnesia, this time period they can’t remember
gradually shrinks forward, and you recover older memories first, then more recent ones
o There will always be a period of several hours though from before the injury they
permanently can’t remember – page 841
Short term memory – memories that last less than a few minutes
Long term memory – memories that last more than a few minutes
Cerebral contusions caused by head trauma often involve the anteromedial temporal lobes and basal
orbitofrontal cortex
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This causes permanent problems with memory
Concussion is associated with memory loss that’s usually reversible, except for the hours around the
time of the injury
Infarcts or ischemia can cause memory problems, especially when bilateral medial temporal or medial
diencephalic areas are affected
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Both the medial temporal and the medial thalamic areas are supplied by the posterior cerebral
artery
So lesions at the top of the basilar artery can cause either bilateral medial temporal or medial
diencephalic infarcts
Global cerebral lack of oxygen, like in cardiac arrest, can cause memory loss
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This may be due to the hippocampus being vulnerable to hypoxic injury
Rupture of an anterior communicating artery aneurysm can damage the basal forebrain, causing
memory loss along with other frontal lobe problems
Wernicke-Korsakoff syndrome is caused by thiamine deficiency, which happens most often in alcoholics
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They’ll have bilateral necrosis of the mammillary bodies, and other medial diencephalic or
periventricular nuclei
People with thiamine deficiency have ataxia, eye movement problems, and a confused state
Severe thiamine deficiency can cause coma or death
Patients who survive the acute stages of thiamine deficiency get anterograde and retrograde
amnesia, caused by bilateral diencephalic lesions
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People with Wernicke-Korsakoff syndrome also usually have frontal lobe problems
o Includes judgement, initiative, impulse control, and sequencing tasks
Unlike people with “pure” medial diencephalic or temporal lesions, people with WernickeKorsakoff syndrome often are unaware they have any memory problems
o Often they confabulate – means they make up stuff so that they don’t have to admit
they don’t remember
 This is aided by the frontal lobe problems, which causes disinhibition and loss of
self-monitoring abilities
People with tonic-clonic seizures usually have memory loss of events during the seizure and postictal
period (period of time right after the seizure)
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Memory in between seizures though is fine unless the seizures are severe or caused by lesions
of the medial temporal lobe
Electroconvulsive therapy (ECT) is a therapy for depression, where you give them a seizure while they’re
under anesthesia multiple times, which can cause retrograde and anterograde amnesia that goes away
once treatment is over, but leaves a gap of permanent retrograde and anterograde memory loss from
during the treatment period
Transient global amnesia shows development of abrupt retrograde and anterograde amnesia with no
obvious cause
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The episodes come on from physical exertion or emotional stress
During the amnesia, they characteristically ask the same questions over and over, with no
recollection of having asked them a few minutes earlier
The amnesia lasts 4-12 hours, after which they fully recover other than permanent loss for a
period of a few hours before and a few hours after the onset
In most patients, they never have another episode of this
There is no epileptic activity in transient global amnesia
Often they have a history of migraines
In the early stages of several neurodegenerative disorders, especially in Alzheimer’s, there’s memory
loss of recent events
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This may happen because early Alzheimer’s tends to preferentially affect the bilateral
hippocampal, temporal, and basal forebrain structures
In psychogenic amnesia, they forget events with emotional significance, which includes repressing
memories
Infantile amnesia – normal inability for adults to recall events from the first 1-3 years of life
Benign senescent forgetfulness – normal mild decline in memory function gradually over decades
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This is different from Alzheimer’s and other forms of dementia, where memory loss is more
severe and happens over a few years
Dreams can be recalled immediately after waking up from sleep, but often you’ve forgotten them by a
few minutes later
Forgetting – memories become less distinct or may not be recalled
Amygdala – group of nuclei in the anteromedial temporal lobe
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The amygdala has 3 main nuclei: corticomedial, basolateral, and central nuclei
The stria terminalis is also part of the amygdala
Usually the basolateral nuclei is biggest and works to connect the amygdala to cortex areas, the
basal forebrain, and medial thalamus
The corticomedial nuclei work in olfaction and working with the hypothalamus for appetite
The central nucleus is smallest and connects to hypothalamus and brainstem areas for
autonomic control
The amygdala is pivotal for emotion and drives, and connects to the rest of the limbic system to
work in all 4 limbic system jobs (olfaction, memory, emotion, autonomics)
Emotion and drive is controlled by interactions between many brain regions
o Includes the amygdala, heteromodal association cortex, limbic cortex, septal area,
ventral striatum, hypothalamus, and brainstem autonomics and arousal pathways
 The amygdala is the main one
o The amygdala is important for attaching emotional significance to stimuli perceived by
the association cortex
o Seizures affecting the amygdala and nearby cortex cause powerful emotions of fear and
panic
o The amygdala is important in fear, anxiety, and aggression
The septal area is big on pleasurable states
Connections between the amygdala and hypothalamic and brainstem centers for autonomic
control mediate changes in heart rate, peristalsis, gastric secretion, sweating, and other changes
seen with strong emotion
The amygdala is big an attaching emotion to a memory
Page 846 – pics of the amygdala and hippocampal formation
o The amygdala both receives from and projects to the cortex, including the limbic cortex
and heteromodal association areas
o The amygdala has 2 pathways it uses to connect to subcortical areas:
 Stria terminalis – the “long pathway”
 The stria terminalis arcs like a “C” from the
amygdala along the wall of the lateral
ventricle to reach the hypothalamus and
septal area
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One connection it has is to carry olfactory info to the hypothalamus to
affect appetite
Ventral amygdalofugal pathway – the “short pathway”
 The ventral amygdalofugal pathway goes from the amygdala anterior to
the forebrain and brainstem
 Projection to the forebrain works in emotion, motivation, and cognitive
functions
 The ventral amydalofugal pathway also works in homeostasis through
autonomics and neuroendocrine signals with the hypothalamus
Seizure – episode of abnormally synchronized and high-frequency firing of neurons in the brain that
causes abnormal behavior or an abnormal experience
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A seizure is a symptom of abnormal brain function
Epilepsy – disorder where there is a tendency to have recurrent unprovoked seizures
Seizures can happen in normal people when provoked by electrolyte problems, alcohol withdrawal,
electroshock therapy, toxins, and more
“ictal” – means during the seizure
“post-ictal” – means immediately after the seizure
“interictal” – means between seizures
Seizures are classified as either partial or generalized
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Partial (focal, local) seizures – abnormal paroxysmal electrical activity happens in a localized
area of the brain
Generalized seizures – abnormal electrical discharge that involves the whole brain
Seizures can start as partial and then spread to become secondarily generalized
Epilepsy is classified as localization-related (partial, focal, or local) epilepsy, and generalized (primary)
epilepsy
Partial (focal) seizures can be further subdivided into simple partial and complex partial seizures
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Simple partial seizures – consciousness is spared
o Ex: if they started having rhythmic twitching movements from a simple partial seizure,
they’d still be alert, they could still talk during it, and remember it
Partial seizures can have positive symptoms, like hand twitching, or negative symptoms, like language
problems
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Manifestations of partial seizures depend on where in the brain the seizure happens
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Seizures in the primary visual cortex can cause shapes and flashes of lights to show up in the
contralateral visual field
Seizures in visual association cortex can cause visual hallucinations, like scenes or a person’s
face
Seizures in the auditory cortex can cause sounds heard from the direction opposite the
problem cortex
Seizures in auditory association cortex can cause them to hear voices or music
o Musical hallucinations are more common in nondominant hemisphere seizures
Seizure aura – brief, simple partial seizure of any type that doesn’t cause any outward behavioral
manifestations
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They can just happen, or serve as a warning for a larger seizure, which starts as an aura and then
spreads
Seizures from the medial temporal limbic structures often come with an aura of a rising feeling
in the epigastric area (“butterflies in stomach”), déjà vu, strange unpleasant odors, or feelings
of extreme fear and anxiety
o Odor and panic come from the amygdala and nearby cortex
Seizures in the primary motor cortex usually have simple rhythmic jerking clonic movements, or
sustained tonic contractions in the contralateral extremities
Seizures in the frontal motor association cortex can cause more elaborate movements, like the
characteristic “fencing posture” (extension of contralateral arm), bilateral leg cycling movements,
turning of the eyes, head, or whole body, and making unusual sounds
A typical simple partial seizure is 10-30 seconds, but they can be longer or shorter
Brief, simple partial seizures usually have no problems after the seizure
If the seizure is prolonged or recurrent, there may be post-ictal depressed function of th local region of
cortex involved, causing focal weakness, called Todd’s paresis, or other problems
Unlike simple partial seizures, complex seizures have impaired consciousness
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It’s thought this is cause the seizure activity affects more of the cortex
Impairment of consciousness can be complete or mild
The most common site for complex partial seizures is the temporal lobes, causing temporal lobe
epilepsy (aka psychomotor epilepsy)
Medial temporal lobe complex partial seizures usually start with an aura of unusual or
indescribable sensation, or with epigastric, emotional, or olfactory phenomena, or déjà vu
o This is followed by unresponsiveness and loss of awareness
 During this they can show automatisms, which are repetitive behaviors like lip
smacking, swallowing, or hand or leg movements like stroking, wringing, or
patting
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Often the ipsilateral basal ganglia are involved in the temporal lobe seizure, causing
contralateral dystonia or immobility, while the ipsilateral extremities show
automatisms
Other symptoms may be bland staring, and autonomic stuff like tachycardia, and pupil
dilation
The typical duration of a medial temporal lobe complex partial seizure is 30 seconds to 2
minutes
Posti-ictal problems can last minutes to hours and include headache, unresponsiveness,
confusion, amnesia, tiredness, agitation, aggression, and depression
Partial seizures in the lateral temporal lobe show more auditory symptoms, like vertigo, problems
hearing, auditory hallucinations (like buzzing, voices, or music)
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Aphasia suggests its the dominant lateral temporal lobe
Saying words or phrases repeatedly and musical hallucinations suggest nondominant lateral
temporal lobe seizure
Frontal lobe partial complex seizures usually show more motor and muscle symptoms, like contralateral
tonic-clonic activity (primary motor cortex), strong turning of eyes, head, or body away from side of the
seizure (prefrontal cortex), fencing posture of contralateral extremity (supplemental motor area), motor
automatisms, and making unusual sounds
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Frontal lobe partial seizures are usually brief, happen multiple times per day, and have no postictal problems
Occipital lobe partial seizures show vision symptoms like sparkles, flashes, lights, scotoma, hemianopia
and visual hallucinations
The most common type of generalized seizure is a generalized tonic-clonic seizure (aka grand mal
seizure)
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A grand mal seizure can be generalized from the start, or begin focally and then spread to
become generalized
It starts with a tonic phase characterized by loss of consciousness and generalized contraction of
all muscles, lasting for 10-15 seconds
o This often causes stiff extension of the extremities, which can lead to a fall, and a
characteristic expiratory gasp or moan can happen as air is forced past the closed
glottis
Next is a clonic phase, characterized by rhythmic bilateral jerking contractions of the
extremities, that then gradually slow and then stop
o Incontinence or tongue biting is common
o There is usually a massive ictal autonomic effect of tachycardia, hypertension,
hypersalivation, and pupil dilation
The grand mal seizure usually lasts 30 seconds to 2 minutes
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Immediately post ictal, they lie immobile, flaccid, and unresponsive, with eyes closed, and are
breathing deeply to compensate for the acidosis the seizure caused
After a few minutes they start to move and respond
Post-ictal problems last from minutes to hours, and include being tired, confused, amnesia, and
headache
Other types of generalized seizures are uncommon
Absence (petit-mal) seizures are generalized seizures that are brief episodes of staring and
unresponsiveness lasting for about 10 seconds
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There are no post-ictal problems, except for lack of awareness of what happened during the
time of the seizure
Petit-mal seizures show a characteristic generalized spike and wave (dome) discharge on EEG
Absence seizures are most common in childhood, and can happen many times per day
Absence seizures can be provoked by hyperventilation, strobe lights, or sleep deprivation
Page 852 – difference between the staring seen in medial temporal complex partial seizures, and
absence seizures
When any type of seizure happens either continuously or repeatedly in rapid succession, it’s called
status epilepticus
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Generalized tonic-clonic status epilepticus is a medical emergency that needs immediate
treatment
o First line therapy is benzodiazepines and phenytoin
The first step in diagnosing a seizure is to figure out if they’re epileptic seizures, or just a random one
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Epileptic seizures are usually brief and stereotyped to happen the same way each time in the
patient
Page 853 – causes of seizures
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The risk for new onset seizures is high in kids, declines in adulthood, and then rises again in the
elderly
The most common causes of seizures in kids are febrile seizures, congenital disorders, and
perinatal injury
The most common cause of seizures in people over 60 is cerebrovascular disease
The risk for a seizure after head trauma increases with how severe it was
o Minor injuries don’t show much risk for seizure
Hypoglycemia and electrolyte changes can trigger seizures
Febrile seizures are common in kids
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Febrile (involve a fever) seizures are usually brief generalized tonic-clonic seizures called simple
febrile seizures, which don’t increase the risk for epilepsy
Complex febrile seizures – seizures lasting more than 15 minutes, or happening more than once
in 24 hours
o Complex febrile seizures can cause epilepsy
Prolonged febrile seizures can cause temporal lobe epilepsy by medial temporal sclerosis
o Once established, there is often a latent period of up to several years until complex
partial seizures start up
o Removing part of the medial temporal lobe cures most of these
Rolandic epilepsy – common cause of focal, mostly nocturnal seizures in kids that is inherited
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Rolandic epilepsy shows characteristic centrotemporal spikes on EEG
Rolandic epilepsy first shows up from age 3-13, and the seizures are often mild
Most affected people then stop getting the seizures by age 15
The basic goal of treating epilepsy is to reduce the risk of seizures while minimizing side effects, in order
to get the best possible overall quality of life
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¾ of epilepsy can be treated with drugs to control seizures
1/3 of epilepsy has seizures that can’t be controlled well by drugs, so they’re called medically refractory
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These people are candidates for epilepsy surgery
o It works best when the seizures are localized, especially when it’s localized to the
temporal lobe, so you just take that part out
Angiogram Wada test – inject them at the common carotid artery with the sedative sodium
amytal and inhibit one hemisphere at a time, looking for aphasia, to see which one is dominant
o Memory is also tested – it should be fine no matter which side you inject
 If you get memory loss, the contralateral medial temporal lobe is affected
o The common carotid perfuses the anterior and middle cerebral artery areas, but not the
posterior cerebral artery area
If multiple parts of a single hemisphere are affected, and they’re under 2-3 years old, you can do
a hemispherectomy and remove that whole hemisphere
o Before this age, neither side is dominant yet and processes are still developing, so the
other side can become dominant and develop normal function
Neurostimulation can be done by placing vagus nerve stimulators in their head, which then
chronically stimulates the vagus nerve at a set rate, and can also be triggered by the patient or
others externally to stop a seizure by using a magnet
o Vagal afferents go to the nucleus solitarias, and are relayed to the limbic system and
other forebrain stuff
Schizophrenia – people with schizophrenia have delusions, hallucinations, disorganized tangential
speech, flat affect, and catatonia (decrease in spontaneous activity)
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Schizophrenics also often have problems with memory
It’s likely that schizophrenia is from too much dopamine, because symptoms get better when
you give them dopamine blockers
Obsessive-compulsive disorder – they have recurrent, intrusive obsessive thoughts that cause them
anxiety, and so they do repetitive, compulsive behaviors to provide temporary relief
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It’s thought OCD is from a decrease in serotonin, because giving them drugs that increase
serotonin helps
The basal ganglia may be involved, especially the caudate, cingulate gyrus, and orbitofrontal
cortex
Anxiety disorders include panic disorder, phobias, posttraumatic stress disorder, and generalized anxiety
disorder, and OCD
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Anxiety is thought to be associated with an increase in norepinephrine and serotonin systems
in the CNS
Anxiety symptoms can be controlled with benzodiazepines, which act on GABA receptors
Symptoms of anxiety, panic, and fear are accompanied by increased peripheral symp tone and
increased release of epinephrine from the adrenals
Depression – sad, don’t enjoy things, impaired concentration, increased or decreased sleep, appetite,
level of activity, feeling worthless, or suicidal
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Depression involves decreases in norepinephrine and serotonin
Almost half of people with severe depression have increased release of cortisol from increased
corticotropin-releasing hormone from the hypothalamus
Mania – abnormally increased irritable mood, with decreased sleep, pressured speech, racing thoughts,
easily distracted, increased activity, and impulsive behavior