Neuroanatomy Flashcards
3 main components of the brain
forebrain (cerebral hemispheres and dienchephalon), midbrain, and hindbrain (medulla, pons, cerebellum)
rostral/caudal in the brain
anterior/posterior
horizontal plane synonym
axial plane. parallel to the floor
sagittal plane
perpendicular to floor, from forehead to occiput; much like an archer shooting a bow
unimodal vs. polymodal cortex
unimodal: processes information pertaining to a specific sensory modality. plays a prominent role in perception.
polymodal: processes information received from disparate modalities through afferent connections. critically involved in higher-order conceptual processes that are less dependent on concrete sensory information than on abstract features extracted from multiple inputs. examples: Convergence zones of the anterior temporal lobe and inferior parietal lobule.
3 divisions of the frontal lobe
- orbitofrontal/ventromedial region: important for emotional regulation, reward monitoring, and personality; damage to the orbitofrontal sector produces disinhibition, whereas damage to the ventromedial sector results in disordered reward/punishment processing and problems marking perceptual or learning experiences with reward value and emotional significance.
- dorsolateral region: important for broad range of cognitive-executive functions; damage produces dysexecutive syndromes, impairments in working memory, and poor attentional control of behavior
- dorsomedial region: important for intentional and behavioral activation; extensive damage to this region produces striking impairments in initiated behavior including akinetic mutism
akinetic mutism
a person is alert and awake (not comatose) but cannot move or speak. results from bilateral frontal lobe injury. can be seen in stroke, tumors of the olfactory groove, and in the final stage of certain neurodegenerative diseases.
3 divisions of the temporal lobe
- temporal polar cortical areas: a polymodal convergence zone important for intersensory integration and semantic memory.
- ventral temporal areas: important for object recognition and discrimination; bilateral damage can produce object or face agnosia
- posterior temporal region: comprised of the middle and superior temporal sulci, which contains the primary auditory areas and Wernicke’s area in the language-dominant hemisphere, important for language comprehension, and prosodic comprehension in the homologous non-dominant hemisphere
3 divisions of the parietal lobe
- superior parietal lobe: important for sensory-motor integration, body schema, and spatial processing
- temporoprietal junction: important for phonological and sound-based processing; language comprehension (left) and music comprehension (right)
- inferior parietal lobule: important for complex spatial attention, integration of tactile sensation, and self-awareness
Occipital lobe contents
- primary visual cortex - surrounds the calcarine fissure (located on caudal end of the medial surface)
- visual association cortex
Complete damage to the primary visual cortex
produces cortical blindness
or
(rarely) Anton’s syndrome (denial of cortical blindness)
or
blindsight (detection of unconsciously perceived stimuli in the blind field)
Partial damage to the primary visual cortex
visual field defects that reflect the region of visual cortex damaged
2 main visual-cortical pathways
ventral visual pathway: connects occipital and temporal lobe and thereafter to anterior portions of inferotemporal cortex; important for object and face recognition, item-based memory, and complex visual discrimination. it processes structural and feature-based information important for the analysis and recognition of visual form such as faces and objects.
Dorsal visual pathway: connecting the occipital and parietal lobes via the superior temporal sulcus; important for spatial vision (processes spatial information) and visuomotor integration (e.g., reaching, manipulating objects)
neocortex
(synonyms: isocortex, 6-layered cortex, neopallium) is part of brain that commands higher functions
6-layer laminar structure distinguishes it from limbic cortex (archicortex), which has only 3
Important Brodmann areas
52 total distinct regions based on microscopic cytoarchitectonic features.
- 44: language-dominant hemisphere is Broca’s area. important for planning of articulatory speech movements (and 45)
- 21: in the inferotemporal region is important for auditory processing (on lateral surface)
- 22: Wernicke’s area (posterior 22
- 41,42: Heschl’s gyrus = primary auditory cortex
39: angular gyrus
40: supramarginal gyrus
Disconnection Syndromes and functional systems
functional system: an interconnected group of cortical and subcortical structures that each contribute important components of a complex behavior or skill. complex behaviors such as memory or language can be impaired by damage to the processors themselves or by damage to their connecting fibers. when damage affects a specific processor, the resulting deficit reflects a loss of that processor’s contribution to the complex behaviors supported by the system.
when damage affects the interconnections among processors, a disconnection syndrome results. disconnection syndromes occur when fiber damage causes functional processors to lose their ability to coordinate or communicate in performing a complex task or behavior.
Geniculostriate visual pathway
primary visual pathway.
Retinal ganglion cells in each eye send their axons into the optic nerve, which projects posteriorly and comes together at the optic chiasm, where the optic tracts originate. the majority of optic tract fibers terminate in the lateral geniculate nucleus (LGN) of the thalamus, which then projects to the primary visual cortex in Brodmann area 17 (striate cortex) in the occipital pole. This is termed the “geniculostriate pathway” and is critical to visual discrimination and form perception.
Extrageniculate or extrastriate visual pathway
a small proportion of optic tract fibers bypasses the lateral geniculate nucleus (LGN) and terminates in the pretectal area (region of neurons found between the thalamus and midbrain) and superior colliculus (midbrain structure). Pretectal and collicular fibers then project to broad areas of parietal and frontal association cortex (including frontal eye fields, BA 8) via relays in the pulvinar nucleus of the thalamus. This “tectopulvinar” system subserves the pupillary light reflex, attention-directed eye movements, and general orientation to visual stimuli and is more sensitive to movement than to form.
the cortical representation of vision
cortical vision is the product of complex parallel processing of multiple, anatomically separate visual input “channels” that compute form, motion, and color. The fact that these “channels” are anatomically distinct means that form, motion, and color processing can be selectively impaired in focal brain disease.
Impairments seen in more dorsally placed lesions vs. ventrally placed lesions
dorsal lesions: may see impairments in spatial perception, attention, and visuomotor processing (e.g., hemispatial neglect, impaired visual reaching, etc.)
ventral lesions: may see perceptual disturbances and, in severe forms, disorders of recognition of familiar objects and/or faces, known as agnosias.
Apperceptive vs. associative agnosia
apperceptive: when a disorder results from impairment in processing basic visual elements of objects (e.g., shape, contour, depth), the disorder is apperceptive in nature. results from extensive damage to visual association areas. they may be unable to draw a picture of an object.
associative: when the recognition disorder results from relating a well-perceived stimulus to stored representations based on prior experience with the stimulus. may result from less extensive or disconnecting lesions in the regions between association cortex and memory. they cannot match an object with their memory. they can accurately describe an object and even draw a picture of the object, but are unable to state what the object is or is used for. but if told verbally what the object is, they could describe what it is used for.
damage causing amnesic syndrome
can result from focal damage to the medial temporal lobes, the medial diencephalon, or the basal forebrain (parts of an integrated, distributed memory system)
neuroanatomy of the hippocampus
dentate gyrus
sectors of Ammon’s horn (cornu Ammonis [CA] 1-4)
subiculum
Trisynaptic circuit
The primary internal connections of the hippocampus
entorhinal cortex > dentate granule cells [synapse 1] > CA3 via mossy fibers [synapse 2] > CA1 via Schaffer collaterals [synapse 3]. CA1 neurons project to the subiculum which is the major source of hippocampal cortical efferent projections. the subiculum projects back to the entorhinal cortex, completing the circuit. described as unidirectional but non-human primate and rodent studies suggest bidirectional reciprocal connections between the hippocampus, entorhinal cortex, and other extrahippocampal structures.
Primary cortical inputs into the hippocampus
Ventral Stream > unimodal (primarily visual) cortical areas > perirhinal cortex >lateral (anterior) entorhinal cortex > both HC CA1 and CA3
Dorsal Stream > Parietal and Frontal Association Areas > Parahippocampal cortex > Medial (posterior) Entorhinal Cortex > Both HC CA1 and CA 3
(see stucky page 35 for review)
newer findings suggest that both the parahippocampal and perirhinal cortices have spatial and non-spatial cortical connections and communication occurs between the two areas, allowing both structures to access both types of information from the cortex prior to their interaction with the hippocampus.
the posterior/medial medial entorhinal cortex receives a majority of its input from the parahippocampal cortex and “spatial” cortical regions. the posterior medial entorhinal cortex evidences greater spatial-specific function compared to the anterior lateral entorhinal cortex due to the presence of grid cells which encode for spatial location in the environment and communicate with the place cells of the hippocampus.
3 main subcortical projections from the hippocampus to structures outside of of the temporal lobe memory circuit
- fibers from CA1, CA3, and subiculum project in the precommisural fornix to the lateral septal nucleus
- subicular projections travel in the postcommisural fornix and terminate on the mammillary bodies or the anterior nucleus of the thalamus. (this was part of Papez circut to explain how the hypothalamus and cortex coordinate emotion-cognition interaction)
- the hippocampus also projects to the amygdala, nucleus accumbens, other regions of the Basal Forebrain, and ventromedial hypothalamus.
Papez circuit: remaining part after #2- is the medial limbic circuit.
Perirhinal/Parahippocampal cortex > hippocampus > fornix pathway leads to mamillary bodies > takes mammillothalamic tract to anterior thalamus > cingulate gyrus > back to hippocampus via cingulum and parahippocampal cortex.
Lateral Circuit: Perirhinal/Parahippocampal cortex > amygdala > ventral amygdalofugal pathway to Dorsomedial thalamus > orbitofrontal > amygdala via the uncinate fasciculus.
can also go from PPC > straight to dorsomedial thalamus
Two-System Theory of Amnesia
amnesia occurs when both the lateral and medial limbic circuit are damaged. e.g., if lesions affect the fornix (medial circuit) and ventral amygdalofugal pathway (lateral circuit), severe amnesia occurs. if only one area is affected, affecting one pathway, a less severe memory disturbance results.
studies suggest that structures within each of the two memory systems are highly interdependent, since damage to different parts of each system can cause apparently equivalent deficits and 2) that each system can, to a large extent, carry on the function of the other, since lesions affecting only one system can result in memory loss that is far less severe than if both systems are damaged.
4 primary conclusions:
- damage to cortical and subcortical structures within the temporal lobe, whether focal or extensive, can result in amnesia.
- amnesia most likely results from damage to both the hippocampally based medial limbic circuit and the amygdala-based lateral limbic circuit
- damage to individual elements of these circuits can all result in amnesia, provided that both circuits are damaged
- the hippocampus appears critical for episodic memory, whereas the amygdala appears more directly involved in emotional aspects of cognition, including emotional memory and assigning emotional significance to stimuli
Thalamus
(meaning “inner chamber” or “bedroom” in Greek)
in addition to sensory information, the thalamus also conveys nearly all other inputs to the cortex, including motor inputs from the cerebellum and basal ganglia, limbic inputs, widespread modulatory inputs involved in behavioral arousal and sleep-wake cycles, and other inputs.
important as a sensory relay nucleus but also has critical functions in higher cognitive processes including alertness, behavioral activation, and memory.
comprised of nuclear groups separated in the ventral-dorsal and anterior-posterior places by a system of myelinated fiber tracks called the internal medullary lamina (IML). it is within the IML that memory-relevant fibers of the mammillothalamic tract and the ventral amygdalofugal pathways travel on their way to their terminations in the anterior and dorsomedial thalamic nuclei, respectively.
-Amnesia is more associated with lesions affecting the internal medullary lamina and mammillothalamic tract. more posterior lesions that involve portions of the dorsomedial nucleus but spare the IML and mammillothalamic tract are not associated with amnesia
Alternate explanations of thalamic amnesia involving midline thalamic nuclei
midline thalamic nuclei have connections with the hippocampus and are consistently damaged in patients with Wernicke-Korsakoff disease. Aside from impairing connections to the hippocampus, thalamic lesions may disconnect thalamic connections with the frontal lobes. it has also been proposed that restricted thalamic lesions in Wernickes might disconnect dorsomedial-frontal connections important for imposing cognitive structure on semantic memories resident in posterior cortex.
Basal Forebrain
3rd major region essential for normal human memory function. It is the major source of cholinergic input throughout the brain. Damage here is associated with profound memory loss with confabulation, the latter of which is likely associated with neighboring frontal lobe damage.
components include the septal area, diagonal band of Broca, nucleus accumbens septi, olfactory tubercle, substantia innominata (containing the nucleus basalis of Meynert), bed nucleus of the stria terminalis, and preoptic area.
Cause of memory loss after Anterior Communicating Artery hemorrhage
thought that damage to cholinergic neurons in the basal forebrain from the hemorrhage (which project to both the medial and lateral limbic circuits) may be responsible.
it may not be the size of basal forebrain lesions that matter for causing amnesia, but whether the lesion is situated to produce a cholinergic disconnection with memory-relevant structures in the diencephalic and medial temporal lobe memory systems.
Language Hemisphere Dominance
Left hemisphere dominant for 95% of right-handers and in more than 60-70% of left-handers.
Fluent aphasias
Affected areas: Wernicke’s area and adjacent BA 37 (medial and lateral most caudal portion of temporal lobe- includes part of fusiform gyrus) ,39 (angular gyrus), and 40 (supramarginal gyrus)
these areas are responsible for initial perceptual steps of language processing enabling phonological (sound-based) sequences to be identified and comprehended as words. damage produces a fluent aphasia (because motor-articulatory regions in the frontal lobe are intact) characterized primarily by a disturbance in comprehension (wernicke’s aphasia).
Nonfluent aphasias
articulation of speech sounds and production of words and sentences depends on a variety of regions including the face area of the primary motor cortex, but begins in Broca’s area, which plans and activates sequences of speech sounds. damage to this region produces a nonfluent aphasia with relatively intact comprehension, known as Broca’s aphasia and it’s variants.
Conduction Aphasia
disturbance of repetition and spontaneous speech, phonemic paraphasia. Deficit: disconnection between sound patterns and speech production mechanisms. lesion location: arcuate fasciculus.
Repetition of language requires that the phonological representations generated by processing in Wernicke’s area be converted to motor-articulatory sequences and utterances in Broca’s area. The two regions are connected by a large subcortical white matter pathway, the arcuate fasciculus, which is volumetrically larger in the left hemisphere than in the right. damage restricted to the arcuate fasciculus produces a disproportionate deficit in repetition, with relative sparing of comprehension and fluency, a syndrome known as conduction aphasia.
Arcuate Fasciculus
a large subcortical white matter pathway connecting Broca’s and Wernicke’s areas, which is volumetrically larger in the left hemisphere than in the right. damage restricted to the arcuate fasciculus produces a disproportionate deficit in repetition, with relative sparing of comprehension and fluency, a syndrome known as conduction aphasia.
Prosody
defined as the use of tone, pitch, rhythm, and other vocal intonation patterns to convey both meaning (e.g., marking a question vs an exclamation) and emotion (e.g., marking specific states such as anger, sadness, or mirth) in language. Prosody is primarily processed in the right hemisphere, where focal leions can produce prosodic syndromes (aprosodias) that bear striking similarity to their contralateral language-based counterparts. E.g., damage to the inferior right frontal lobe produces a deficit in expressing emotional prosody in speech that is analogous to Broca’s aphasia, while posterior temporal-parietal lesions produce a deficit in prosody comprehension with fluent production, akin to Wernicke’s.
Broca’s Aphasia
decreased speech production; sparse, halting speech, missing function words, syntactic deficits, right hemiparesis (often). Deficit: Impaired speech planning and production. Lesion: posterior aspect of third frontal convolution- BA 44,45 (damage to adjacent motor fibers may produce right hemiparesis)
Wernicke’s aphasia
decreased auditory comprehension, fluent speech, paraphasias, poor repetition and naming, may have right homonymous hemianopia Deficit: impaired representation of the sound structure of words. lesion location: BA 22. posterior half of the superior (first) temporal gyrus (geniculostriate white matter damage may produce right homonymous hemianopia)
Anomic Aphasia
decreased single word production, marked for common nouns; repetition and comprehension relatively intact. Deficit: impaired storage or access to lexicon. Lesion: Inferior parietal lobule or connections within perisylvian language areas; many other forms of aphasia evolve to anomia in recovery
Transcortical Motor Aphasia
disturbed spontaneous speech similar to Broca’s; relatively preserved repetition and comprehension. Deficit: disconnection between conceptual word/sentence representations in perisylvian region and motor speech areas. Lesion: deep white matter tracts connecting broca’s area to parietal lobe; usually caused by anterior watershed infarcts
Transcortical Sensory Aphasia
disturbance in word comprehension with relatively intact repetition. Deficit: disturbed activation of word meanings despite normal recognition of auditorily presented words. Lesion: white matter tracts connecting parietal and temporal lobe. usually caused by posterior watershed infarcts.
Alexia without agraphia
damage to the interhemispheric crossing fibers in the splenium of the corpus callosum. these lesions prevent information that was appropriately perceived in the right hemisphere/left visual field from accessing the perisylvian language areas in the left hemisphere. can also cause color agnosia (color naming disturbances), and optic aphasia.
Optic Aphasia
person cannot name a visually apprehended object but can demonstrate its use, presumably because more anterior callosal fibers connecting the intact visual areas to left hemisphere praxis mechanisms are intact.
Pure word deafness
the patient cannot understand language but can identify nonverbal sounds such as chirping birds or jingling keys. results from white matter disconnection of fibers from left and right auditory receptive areas (Heschel’s gyrus, BA 41,42 in each hemisphere) from Wernicke’s area in the left hemisphere.
Cortico-striatal-pallidal-thalamo-cortical loop
an essential feature of cortical-subcortical interaction in a variety of cognitive domains. Cortical activity is modulated by connections from cortex, through inhibitory and excitatory structures in the basal forebrain and thalamus, and back to cortex as a way of engaging a cortical region needed for task performance or of inhibiting another region whose function would interfere with processing or compete for output. The process of activating cortical regions for task performance is known as selective engagement.
cortex > striatum (caudate, putamen) > globus pallidus > thalamus >Back to cortex
Selective Engagement
The process of activating cortical regions for task performance, heavily involves the frontal lobe and subcortical interactions
Posner and Rothbart (2007)’s 3 interconnected systems for attention
- orienting to stimuli- tuning of perceptual systems to incoming stimuli so that relevant information from sensory input can be selected for further processing. dependent on acetylcholine and involves a functional system consisting of the superior colliculus, pulvinar thalamic nucleus, posterior temporoparietal cortex, and a region within the frontal lobes known as the frontal eye fields (BA 8, involved in volitional control of eye movements).
- alerting: a state of sensitivity to incoming stimuli. it is modulated by norepinephrine and depends primarily on ascending sensory inputs from the thalamus.
- executive aspects of attention: executive attention involves monitoring and resolving conflicts among thoughts, feelings, and behaviors. it is primarily dependent on dopamine and involves key structures including the anterior cingulate cortex and DLPFC.
Mechanisms of complex attentional acts
a combination of bottom-up and top-down influences. Sensory signals first arrive at superior colliculi and pulvinar for preprocessing in a “bottom-up” information processing that is biased toward salient environmental stimuli and is then sent to frontal and parietal cortices. In turn, “top-down” biases from parietal (which provides visuomotor frames of reference) and frontal lobe (which provides substrate for working memory and goal setting) are transmitted to colliculi, pulvinar, and frontal eye fields, such that any complex attentional act is a combo of bottom-up and top-down processes.
research suggests a dorsal frontoparietal system forms the cortical substrate of top-down attention, whereas a more ventral frontoparietal system is involved in target detection in the sensory environment.
Working Memory Neural Substrates
seminal work by Goldman-Rakic with primate studies. functionally separate working memory subsystems exist in the dorsolateral PFC.
- a dorsal (spatial)-ventral (object-based) distinction appears to exist in frontal working memory systems just as it does in posterior cortex.
- dorsal components of the frontal working memory system are preferentially connected to structures in the dorsal visual stream and vice-versa. Neuronal subpopulations in the dorsal prefrontal cortex (arcuate sulcus; BA46) code spatial information, whereas others in the ventral prefrontal cortex (inferior prefrontal convexity; BA12) are selectively active during object working memory tasks.
Acetylcholine
Main function in the CNS is the facilitation of attention, memory, and learning. Pharmacological blockade of central cholinergic transmission causes delirium and memory deficits. degeneration of cholinergic neurons in the basal forebrain may be one of the mechanisms for memory decline in Alzheimer’s disease.
2 main origins:
1.) pontomesenchephalic region > projects to intralaminar nucleus of thalamus > then to widespread areas of the cortex. role: indirect excitation of thalamo-cortical projection. affects attention, memory, regulation of thalamic output
- basal forebrain region (nucleus basalis of meynert; medial septum; nucleus of the diagonal band) > widespread cortical (meynert) and hippocampus (medial septum and diagonal band). Role is exciation/facilitation. affects attention, learning, and memory
2 subclasses of acetylcholine-containing receptors.
1. muscarinic: mediate the main cognitive effects attributed to cholinergic pathways, with effects on attention, learning, and memory.
2. nicotinic: trigger rapid neural and neuromuscular transmission within the sympathetic and parasympathetic nervous system and at the neuromuscular junction.
drugs with strong anticholinergic properties (e.g., antihistamines, first-generation antipsychotics, and tricyclic antidepressents) thus may exert negative effects on cognitive performance in these areas, particularly when administered to elderly or others with reduced cognitive and or cerebral reserve.
Norepinephrine (Noradrenaline)
2 origins:
1.locus coeruleus (small brainstem nucleus, latin for blue spot)> widespread cortical. role excitation/facilitation. affects attentional shifting; arousal
- lateral tegmental area of pons and medulla > widespread cortical. role excitation/facilitation. affects mood; sleep-wake cycle
these projections can be inhibitory or excitatory. has been called a “stress hormone,” plays a role in attention, sleep-wake cycles, and mood and may have a modulating role in pain. it plays a role in neuropsychiatric disorders such as depression, bipolar disorder, and in anxiety disorders such as OCD.
cholinergic and serotonergic activation can inhibit NE neurotransmission. drugs commonly prescribed for ADHD (methylphenidate [Ritalin, Concerta], amphetamine/dextroamphetamine [Adderall] increase levels of NE and dopamine, whereas atomoxetine (Strattera) is a specific norepinephrine reuptake inhibitor that only affects NE.
Serotonin
2 origins:
1. Rostral raphe nuclei of midbrain, pons, and medulla > forebrain (thalamus, basal ganglia, cortex). role is post-synaptic inhibition. affects mood and arousal
plays a role in psychiatric syndromes including anxiety, depression, OCD, aggressive behavior, and certain eating disorders.
- dorsal raphe >cerebellum, medulla, spinal cord. role is post-synaptic inhibition. affects pain, respiration, temperature, motor control.
drugs affecting serotonin metabolism are commonly prescribed for depression, generalized anxiety, and social phobia. Some (e.g., fluoxetine [Prozac], sertraline [Zoloft] are serotonin-specific reuptake inhibitors, wheras others (e.g., venlafaxine [Effexor]) effect reuptake inhibition in the serotonergic and noradrenergic system. These drugs can be used in combo with serotonin 2A antagonists (e.g., trazodone [Desyrel], mirtazapine [Remeron], or other agents to treat refractory depression.
Dopamine
dopamine-containing neurons exist primarily in the substantia nigra pars compacta and in the ventral tegmental area of the midbrain.
Projection system is generally organized into 3 separate subsystems:
1. Mesostriatal system arises from the substantia nigra pars compacta and projects to the striatum (caudate and putamen). this pathway is implicated in Parkinson’s and dysfunction here can produce disabling motor and nonmotor symptoms. Often PD is treated with dopaminergic agonists.
- Mesolimbic pathway originates in the VTA and projects to the medial temporal lobe, amygdala, cingulate gyrus, and nucleus accumbens. plays a key role in reward functions and has been implicated in addictive behavior. overactivity of this pathway has been associated with the positive symptoms of schizophrenia, such as delusions and hallucinations, which respond well to domaine-seratonin 2A antagonist drugs (e.g., clozapine [Clozaril}, quetiapine {seroquel], risperidone {Risperdal}).
- Mesocortical system arises mainly from VTA and projects primarily to cortical regions of the frontal lobe. This system plays a key role in executive functions, working memory, top-down attention, and initiation of motor activity. dysfunction in this system can produce some of the negative symptoms of schizophrenia, as well as dysexecutive syndrome and bradykinesia.
GABA: Gamma-aminobutryic acid
GABA is one key inhibitory (rather than excitatory) transmitter of signicant importance to memory, anxiety/arousal, and neuromodulation. GABA-ergic neurons (widely distributed)participate in short- and long-range inhibitory projections that innervate many of the same areas as other neurotransmitters and provide counteracting inhibitory input. The balance of GABA-ergic influences, together with the action of other neurotransmitters, is a key basis of neuromodulation. It is generally believed that certain GABA-ergic neurons located in the reticular nucleus of the thalamus may be critical for gating thalamocortical interactions and for regulating sleep and arousal. Similarly, GABA-ergic neurons in the basal forebrain regulate attentional shifting and alternation between response-reinforcement contingencies. Many antianxiety drugs act to enhance GABA-ergic neurotransmission, thus offsetting abnormally strong excitatory influences in these disorders.
Glutamate
(widely distributed. role is post-synaptic excitation). this is the most abundant excitatory neurotransmitter in the brain. plays a key role in learning and memory, and the glutamatergic NMDA receptor is implicated in processes of long-term potentiation and synaptic plasticity/neurogenesis, keys to the development of new experience-dependent memories. The CNS has well-developed mechanisms for rapid removal of glutamate from the synapse because excess glutamatergic activity can lead to excitotoxicity and cell death, and it is part of the ischemic cascade that has been implicated in stroke and in neurodegenerative diseases such as AD and ALS.
Memantine (Namenda), an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely prescribed for the treatment of AD. It may seem paradoxical that antagonizing a receptor that is important in learning and long-term potentiation would be of benefit, but it may be able to enhance cognition by selectively inhibiting pathological aspects of glutamatergic activation while preserving the physiological activation of NMDA receptors, thus restoring LTP.
Visual agnosia
rare neurological disorder characterized by the total or partial loss of the ability to recognize and identify familiar objects and/or people by sight. This occurs without loss of the ability to actually see the person or object. Primary agnosia is associated with bilateral damage to the ventral visual stream, including the lingual and fusiform gyrus.
When a person cannot identify familiar people this is called prosopagnosia. two types of visual agnosia are associative and apperceptive.
neurogenesis
birth and proliferation of new neurons. most active during pre- and perinatal development. in certain regions of the brain (e.g., dentate gyrus and hippocampus), neurogenesis continues into adulthood and is thought to be a critical basis for the formation of new memories and for experience-dependent neuroplasticity.
Neuroplasticity/synaptic plasticity
changes in neural pathways and synapses due to changes in behavior, environment, or neurochemical processes. Neuroplasticity is critical to normal development of CNS-dependent abilities and is critical to recovery from brain damage. the concept of the brain as a “plastic” organ has replaced earlier conceptualizations that no further structural development or repair was possible after a certain point in development and is an important idea in contemporary advancements in recovery of function, neurorehabilitation, and neural repair. The concept of “experience-dependent neuroplasticity” refers to changes that result from exposure to enriched environments, behavioral practice, or other environmental stimulation.
6 laminar layers of neocortex
- Molecular Layer: Main connections: Dendrites and axons from other layers
- Small pyramidal layer/External Granular Layer: Main Connections: Cortical-cortical
- Medium Pyramidal Layer/Internal Granular Layer: Main Connections: Cortical-Cortical
4: Granular Layer/Internal Granular Layer: Main Connections: Receives inputs from thalamus - Large Pyramidal Layer/Internal Pyramidal Layer: Main Connections: Sends outputs to subcortical structures (other than thalamus)
- Polymorphic layer/Multiform Layer. Main Connections:Sends outputs to thalamus.
horizontal plane synonyms
plane parallel to floor. synonyms = axial and transverse
Parts of diencephalon
Diencephalon is part of the forebrain (Prosencephalon) and includes the thalamus, hypothalamus, and supporting structures, such as the epithalamus
Parts of midbrain (mesencephalon)
cerebral peduncles, midbrain tectum, and midbrain tegmentum
The midbrain is relatively short, and most axial sections cut through either the superior colliculi, which are more rostral, or the inferior colliculi, which are more caudal. Sections at these two levels can be distinguished because sections through the superior colliculi also include the oculomotor nuclei and red nuclei, while sections through the inferior colliculi also include the trochlear nuclei and brachium conjunctivum (Decussation of the superior cerebellar peduncles)
Parts of hindbrain (Rhombencephalon)
Metencephalon: Pons and cerebellum
Myelencephalon: Medulla
Inferior Parietal Lobule
made up of the supramarginal gyrus at the termination of the sylvian fissure and th
e angular gyrus
Corticospinal Tract
sometimes called the pyramidal tract bc bc of its triangular shape in the medulla. begins mainly in the primary motor cortex, where neuron cell bodies project via axons down through the cerebral white matter and brainstem to reach the spinal cord. majority (85%) of its fibers cross over to control movement of the opposite side of the body. This pyramidal decussation occurs at the junction between the medulla and the spinal cord. so lesions above the pyramidal decussation produce contralateral weakness with respect to lesion, while lesions below produce ipsilateral weakness.
Upper and Lower Motor Neurons
Motor neurons that project from the cortex down to the spinal cord or brainstem are referred to as upper motor neurons. UMNs form synapses onto the lower motor neurons, which are located in the anterior horns of the central gray matter of the spinal cord or in the brainstem motor nuclei. The axons of the LMNs project of out the CNS via the anterior spinal roots or via the cranial nerves to finally reach muscle cells in the periphery
Two general functions of neurotransmitters
- mediate rapid communication between neurons through fast excitatory (excitatory postsynaptic potentials) or inhibitory (inhibitory postsynaptic potentials) electrical events. these occur on timescales of tens of milliseconds.
- neuromodulation. occurs over slower timescales. includes a broad range of cellular mechanisms involving signaling cascades that regulate synaptic transmission, neuronal growth, and other functions. neuromodulation can either facilitate or inhibit the subsequent signaling properties of the neurons.
Other names with similar meaning for white matter pathways in the CNS
tract, fascicle, lemniscus, bundle
Commissure
white matter pathway that connects structures on the right and left sides of the CNS
afferent vs. efferent
afferent: Pathways carrying signals toward a structure
efferent: pathways carrying signals away from a structure
brachial plexus and lumbosacral plexus
nerves controlling the extremities give rise to elaborate mesworks referred to as the brachial plexus (arms) and lumbosacral plexus (legs). there is also more gray matter in these segments, causing the overall cord thickness to be greater here, called cervical enlargement and lumbosacral enlargement.
Spinal Cord segment organization
Cervical 1-8, Thoracic 1-12, Lumbar 1-5, Sacral 1-5
Sympathetic vs. parasympathetic function
Both controlled by higher centers in the hypothalamus and limbic system as well as by afferent sensory info from the periphery.
Sympathetic: “Fight or flight” Arises from T1 to L3 and releases norepinephrine.
pupil dilation, bronchodilation, cardiac acceleration, inhibition of digestion, piloerection, stimulation of glucose release, systemic vasoconstriction
Parasympathetic: “rest or digest” Arises from the cranial nerves and from S2-4 (craniosacral division) and releases acetylcholine onto end organs
pupil constriction, bronchoconstriction, cardiac deceleration, stimulation of digestion, salivation, lacrimation (tears), intestinal vasodilation
Corpus Callosum
a large c-shaped band of white matter (meaning “hard body”) connecting both homologous and herologous areas in the two hemispheres
consists of the rostrum, genu, body, and splenium
Longitudinal fissure
aka interhemispheric fissure/sagittal fissure. separates the two cerebral hemispheres down the midline
Cingulate gyrus
gyrus surrounding the corpus callosum, running from the paraterminal gyrus anteriorly to the isthmus posteriorly
Cingulate sulcus marginal branch
runs up to the superior surface that forms an important landmark, since the sulcus immediately in front of it, on the superior surface, is the central sulcus. the central sulcus does not extend onto the medial surface but the region surrounding it is called the paracentral lobule
Role of cerebellum and basal ganglia in motor function
These structures do not themselves project directly to LMNs. They act by modulating the output of the corticospinal and other descending motor systems. they both receive major inputs from the motor cortex. the cerebellum also receives significant inputs from the brainstem and spinal cord. then in turn, both areas project back to the motor cortex via the thalamus.
lesions in the cerebellum lead to disorders in coordination and balance, often referred to as ataxia. lesions in the basal ganglia can result hypokinetic movement disorders, such as Parkinsonism, in which movements are infrequent, slow, and rigid, and hyperkinetic movement disorders such as Huntington’s disease, which is characterized by dance-like, involuntary movements.
2 primary somatosensory pathways
- posterior column pathways: convey proprioception, vibration sense, and fine, discriminative touch.
sensory neuron axons arrive first to the spinal cord via the dorsal roots and then travel the ipsilateral white matter dorsal columns to to the dorsal column nuclei in the medulla. here they make synapses onto the secondary sensory neurons, which send out axons that cross over to the other side of the medulla. they ascend now on the contralateral side and synapse in the thalamus, and from there neurons project to the primary somatosensory cortex in the postcentral gyrus. - anterolateral pathways: convey pain, temperature sense, and crude touch.
sensory neuron axons also enter via dorsal roots. however, they make their first synapses immediately in the gray matter of the spinal cord. axons from the secondary sensory neurons cross over to the other side of the spinal cord and ascend in the anterolateral white matter, forming the spinothalamic tract. after synapsing in the thalamus, the pathway again continues to the primary somatosensory cortex.
Thalamus
Important relay center. nearly all pathways that project to the cerebral cortex do so after synapsing in the thalamus. The thalami are grey matter structures. they are located behind the basal ganglia
Hypothalamus
important region for control of autonomic, neuroendocrine, limbic, and other circuits.
Epithalamus
encompasses several small nuclei, including the pineal body, habenula, and parts of the pretectum.
Cranial Nerves
O, O, O, To Touch a Female a Virgin Girl’s Vagina, Ah Heaven
CN I: Olfactory Nerve. olfaction
CN 2: Optic Nerve. vision
CN 3: Oculomotor nerve. Extraocular muscles, except those innervated by CN IV and VI; parasympathetics to pupil constrictor and to ciliary muscles of lens for near vision.
CN 4: Trochlear Nerve: Superior oblique muscle; causes the eye to move downward and to rotate inward (depression and intorsion)
CN 5: Trigeminal Nerve: Sensations of touch, pain, temp, vibration, and joint position for the face, mouth, nasal sinuses, and meninges; muscles of mastication; tensor tympani muscle
CN 6: Abducens Nerve: Lateral rectus muscle; causes abduction (outward movement) of the eye.
CN 7: Facial Nerve: muscles of facial expression; also stapedius muscle and part of digastric; taste from anterior two-thirds of tongue; sensation from a region near the ear; parasympathetics causing lacrimation and supplying the submandibular and sublingual salivary glands
CN 8: Vestibulochoclear nerve: hearing; vestibular sensation
CN 9: glossopharyngeal nerve: stylopharyngeus muscle; taste from posterior one-third of tongue; sensation from posterior pharynx, and from a region near the ear; chemo- and baroreceptors of the carotid body; parasympathetics to the parotid gland
CN 10: Vagus nerve: Pharyngeal muscles (swallowing); laryngeal muscles (voicebox); parasympathetics to the heart, lungs, and digestive tract up to the splenic flexure; taste from epiglottis and pharynx; sensation from the pharynx, posterior meninges, and a region near the ear; aortic arch and chemo- and baroreceptors
CN 11: Spinal Accessory Nerve: Sternomastoid muscle upper part of the trapezius muscle.– head turning
CN 12: Hypoglossal nerve: Intrinsic muscles of the tongue
Reticular formation
important region of the brain stem named for the network-like appearance of its fibers in histological sesctions, the reticular formation extends throughout the central portions of the brainstem from the medulla to the midbrain. the more caudal portions of the RF in the medulla and lower pons tend to be involved mainly in motor and autonomic functions. the rostral reticular formation in the upper pons and midbrain plays an important role in regulating level of consciousness, influencing higher areas through modulation of thalamic and cortical activity.
lesions of the pontomesencephalic RF can cause lethargy and coma
Limbic System
several structures with this name due to location near the medial edge or fringe of the cerebral cortex. has diverse functions, including regulation of emotions, memory, appetitive drives, and autonomic and neuroendocrine control. includes cortical areas located in the medial and anterior temporal lobes, anterior insula, inferior medial frontal lobes, and cingulate gyri. it also includes deeper structures such as the hippocampal formation and the amygdala, located within the medial temporal lobes, several nuclei of the medial thalamus, hypothalamus, basal ganglia, septal area, and brainstem. these areas are interconnected by a variety of pathways, including the fornix.
Fornix
a paired, arch-shaped white matter structure that connects the hippocampal formation to the hypothalamus and septal nuclei
Lesions here can cause deficits in the consolidation of immediate recall into longer-term memories. can cause behavioral changes and may underlie a number of psychiatric disorders. epileptic seizures most commonly arise from the limbic structures of the medial temporal lobe, resulting in seizures that may begin with emotions such as fear, memory distortions such as deja vu, or olfactory hallucinations.
Gerstmann’s Syndrome
Inferior parietal lobule in the left hemisphere: difficulty with calculations, right-left confusion, inability to identify fingers by name (finger agnosia), and difficulties with written language.
Apraxia
abnormalities in motor conceptualization, planning, and execution. motor planning appears to be distributed in many different areas of the cortex. so, diffuse lesions of the cortex, or sometimes more focal lesions affecting the frontal or left parietal lobe, can produce apraxia
Extinction
tactile or visual stimulus is perceived normally when it is presented to one side only, but when it is presented to both sides, the patient neglects the stimulus on the side opposite the lesion. this is a severe abnormality in spatial orientation and awareness. less common in lesions of the dominant parietal lobe, possibly b/c the dominant hemisphere is more specialized in language than it is for visuospatial functions.
Phenomena due to lesions to the visual association cortex
Visual association cortex in the parieto-occipital and inferior temporal lobes—can produce prosopagnosia (inability to recognize faces), achromatopsia (inability to recognize colors), palinopsia (persistence or reappearance of an object viewed earlier).
2 pairs of arteries carrying all blood supply to the brain
internal carotid arteries- form the anterior blood supply
vertebral arteries - join together in a single basilar artery to form the posterior blood supply
they join together in an anastomotic ring at the base of the brain- the circle of willis
-the ACA and MCA derive their main blood supply from the internal carotid arteries (anterior circulation), while the PCAs derive their main supply from the vertebrobasilar system (posterior circulation). vertebrobasilar system also feeds the main arteries supplying the brainstem and cerebellum.
Venous drainage for the brain
b supplied almost entirely by the internal jugular veins
Foramen Magnum
the largest foramen, or hole in the brain where the spinal cord meets the medulla, which is called the cervicomedullary junction
3 Layers of Meninges
from inside out:
- Pia Mater- very thin, adheres closely to the surface of the brain and follows all the gyri and into the depths of the sulci. it also surrounds the initial portion of each blood vessel as it penetrates the brain surface, forming a perivascular space, and then fuses with the blood vessel wall.
- Arachnoid Mater - a wispy, “spidery” meningeal layer that adheres to the inner surface of the dura. within this layer, the cerebrospinal fluid percolates over the surface of the brain.
- Dura Mater: Dura means hard. made of 2 tough, fibrous layers.
mater means mother
Falx cerebri
a flat sheet of dura that is suspended from the roof of the cranium and separates the right and left cerebral hemispheres, running in the interhemispheric fissure.
Tentorium Cerebelli
a tent-like sheet of dura that covers the upper surface of the cerebellum.
3 spaces formed by the meninges
from outside to inside:
- Epidural Space- potential space between the inner surface of the skull and the tightly adherent dura. the middle meningeal artery runs into the epidural space from the external carotid artery and supplies the dura.
- Subdural Space: potential space between the inner layer of dura and the loosely adherent arachnoid. the bridging veins traverse the subdural space. these veins drain the cerebral hemispheres and pass through the subdural space en route to several large dural venous sinuses.
- Subarachnoid Space- the cerebrospinal fluid-filled space between the arachnoid and the pia. in addition to cerebral spinal fluid, the major arteries of the brain also travel within the subarachnoid space and tehn send smaller penetrating branches inward through the pia.
Choroid Plexus
specialized vascular structure that lies inside the ventricles and produces cerebrospinal fluid.
CSF flows from the lateral ventricles through the foramen of monro in each hemisphere, into the third ventricle, through the Sylvian aqueduct, into the fourth ventricle, out through the foramina of Luschka and Magendie, into the subarachnoid space, and up to the arachnoid granulations to be reabsorbed into the bloodstream.
the 4 Ventricles
cavities within the brain that contain cerebrospinal fluid.
- 2 lateral ventricles (one inside each hemisphere)
- Third ventricle (located within the diencephalon). the walls of the third ventricle are formed by the thalamus and hypothalamus.
- fourth ventricle - surrounded by the pons, medulla, and cerebellum.
Cisterns
the subarachnoid space widens in a few areas to form larger CSF collections called cisterns.
Blood-Brain Barrier
the capillary wall endothelial cells in most of the body are separated from each other by clefts, or fenestrations (gaps), allowing relatively free passage of fluids and solute molecules. However, in the brain, capillary endothelial cells are linked by tight junctions forming a blood-brain barrier.
Blood-CSF Barrier
A barrier similar to the blood brain barrier exists between the choroid plexus and the CSF. the capillaries of the choroid plexus are freely permeable, but the choroid epithelial cells form a barrier between the capillaries and the CSF. Lipid-soluble substances, including O2 and CO2, permeate readily across the cell membranes of the BB and B-CSF barriers. However, most other substances must be conveyed in both directions through specialized transport systems, including active transport, facilitated diffusion, ion exchange, and ion channels.
Circumventricular Organs
certain specialized brain regions where the BBB is interrupted, allowing the brain to respond to changes in the chemical milieu of the remainder of the body and to secrete modulatory neuropeptides into the bloodstream. Best known among these are the median eminence and the neurohypophysis, which are involved in the regulation and release of pituitary hormones.
area postrema: the only paired circumventricular organ, located along the caudal wall of the 4th ventricle in the medulla, AKA (chemotactic trigger zone) is involved in detecting circulating toxins that cause vomitting
Area Postrema
AKA: Chemotactic trigger zone
the only paired circumventricular organ, located along the caudal wall of the 4th ventricle in the medulla, is involved in detecting circulating toxins that cause vomitting
Headache
There are no pain receptors in the brain parenchyma itself.
the side of the headache often, but not always, corresponds to the side of pathology.
Most are classified as either a vascular headache or a tension headache.
vascular headache: used to mean migraine as well as the less common but closely related disorder called cluster headaches. thought to involve inflammatory, autonomic, serotonergic, neuroendocrine, and other influences on blood vessel caliber in the head, leading to headache and other associated symtpoms.
In migraine, about 75% of patients have a positive family history, suggesting a genetic basis.
Migraine
type of vascular headache. about 75% of patients have a positive family history, suggesting a genetic basis. often preceded by an aura or warning symptoms, classically involving visual blurring, shimmering, scintillating distortions, or fortification scotoma- a characteristic region of visual loss bordered by a zigzagging lines resembling the walls of a fort. headache is often unilateral, but if it is always on the same side, an MRI scan is warranted to exclude a vascular malformation or other lesion as a trigger for the headaches. pain is often throbbing and may be exacerbated by light (photophobia), sound (phonophobia), or sudden head movement. nausea and vomitting may occur, and the scalp may be tender to the touch. duration is typically 30 minutes to up to 24 hours, and relief often occurs after sleeping.
Treatment is usually quite effective. acute attacks usually respond to NSAIDS, anti-emetics, triptans (serotonin agonists), ergot derivatives, or other medications and to resting in a dark, quiet room.
Preventive measures: avoid triggers when possible, and if they are recurring, treatment with prophylactic agents such as beta-blockers, topiramate, valproate, calcium channel blockers such as flunarizine, tricyclic antidepressants, or NSAIDs
Complicated Migraines
migraines can be accompanied by a variety of transient focal neurologic deficits, including sensory phenomena, motor deficits (hemiplegia), visual loss, brainstem findings in basilar migraine, and impaired eye movements in ophthalmoplegic migraine. This is a diagnosis of exclusion and should be accepted only in the setting of recurrent episodes and only after appropriate tests have been done to exclude cerebrovascular disease, epilepsy, or other disorders
