Midterm 2 Flashcards
1
Q
Explain what the EEG measures, and how it is recorded
A
EEG records the small changes in voltage on the scalp that result from the synchronous synaptic activity of thousands of cortical neurons, especially the pyramidal cells. Electrodes placed on the scalp pick up these minute voltage fluctuations, which are then amplified. The signal reflects currents generated by excitatory synaptic events—primarily the influx of positive ions into dendrites—that create local voltage differences.
2
Q
The amplitude of the EEG signal depends on ?
A
how synchronized the neuronal activity is: more synchronous firing yields larger, rhythmic waves, whereas asynchronous activity results in smaller signals.
3
Q
Identify the EEG frequency band and describe their associations with behavioral and sleep states:
______: High amplitude waves characteristic of deep, slow-wave sleep.
A
Delta (<4 Hz)
4
Q
Identify the EEG frequency band and describe their associations with behavioral and sleep states:
_______: Seen in both sleep and certain waking states.
A
Theta (4–7 Hz)
5
Q
Identify the EEG frequency band and describe their associations with behavioral and sleep states:
_______: Associated with relaxed wakefulness.
A
Alpha (8–12 Hz)
6
Q
Identify the EEG frequency band and describe their associations with behavioral and sleep states:
_________: Observed during periods of active, alert states.
A
Beta (15–30 Hz)
7
Q
Identify the EEG frequency band and describe their associations with behavioral and sleep states:
_________: Linked with attention and active cognitive processing.
A
Gamma (30–90 Hz)
8
Q
Identify the EEG frequency band and describe their associations with behavioral and sleep states:
________: Brief bursts, typically seen in stage 2 NREM sleep, thought to prime cortical networks for memory consolidation.
A
Spindles (12–14 Hz)
9
Q
Identify the EEG frequency band and describe their associations with behavioral and sleep states:
________: Short bouts that, together with other oscillations, contribute to processes like memory replay during sleep.
A
Ripples (80–200 Hz)
10
Q
Describe the importance of synchrony in generating detectable EEG signals?
A
EEG signals are the summed electrical activity from many neurons. For a signal to be strong enough to be detected at the scalp, thousands of neurons must fire in a synchronized manner.
The rhythmic, synchronous activity—often generated by the interplay of excitatory and inhibitory synaptic inputs—results in larger amplitude signals. When neurons fire asynchronously, their individual signals cancel out, resulting in lower amplitude EEG recordings.
11
Q
Summarize how intrinsic properties of thalamic neurons and their network interactions contribute to the generation of rhythmic patterns in EEG recordings.
A
The thalamus serves as a crucial pacemaker for cortical activity. Some thalamic neurons inherently generate rhythmic bursts due to specialized ion channels that allow self-sustained oscillations, even in the absence of rhythmic input.
It also interacts with cortical regions to produce synchronous oscillations—such as sleep spindles—via thalamocortical and reticular connections. These rhythmic bursts help drive the EEG patterns observed in both sleep and awake states.
12
Q
Describe the various stages of sleep, noting the key EEG and physiological changes:
_______: Characterized by a desynchronized (beta) EEG pattern with high-frequency, low-amplitude waves.
A
Wakefulness
13
Q
Describe the various stages of sleep, noting the key EEG and physiological changes:
_______: A transitional phase where alpha rhythms give way to vertex spikes; the person is relaxed but still awake.
A
NREM Stage 1
14
Q
Describe the various stages of sleep, noting the key EEG and physiological changes:
________: Marked by sleep spindles and K complexes, representing a deeper sleep than stage 1.
A
NREM Stage 2
15
Q
Describe the various stages of sleep, noting the key EEG and physiological changes:
_______: Dominated by large-amplitude delta waves; it is the deepest phase of sleep with the lowest physiological activity (e.g., heart rate, blood pressure).
A
NREM Stage 3 (Slow-Wave Sleep, SWS)
16
Q
Describe the various stages of sleep, noting the key EEG and physiological changes:
______: Despite deep muscle atonia, the EEG resembles an awake state with low-amplitude, mixed-frequency waves, accompanied by rapid eye movements and vivid dreaming.
A
REM Sleep
17
Q
A full sleep cycle takes about ____ minutes, with stages shifting over the course of the night to yield progressively shorter _____ periods and lengthened _____ periods.
A
100, NREM, REM
18
Q
Describe the progression from wakefulness through various non-REM (NREM) stages to REM sleep.
A
Wakefulness –> NREM Stage 1 –> NREM Stage 2 –> NREM Stage 3 (SWS) –> NREM Stage 2 –> REM Sleep
19
Q
Explain why sleep is necessary in memory consolidation?
A
During sleep, particularly in SWS, the brain replays recent experiences, transferring and stabilizing memories from the hippocampus to the neocortex.
20
Q
Explain why sleep is necessary in metabolic waste clearance?
A
Sleep facilitates an increase in the brain’s interstitial space, promoting the flow of cerebrospinal fluid (CSF) through the glymphatic system to remove metabolic waste, including amyloid-β, which is implicated in Alzheimer’s disease.
21
Q
Explain why sleep is necessary in overall homeostasis?
A
Sleep modulates physiological functions such as body temperature, hormone release, and immune responses. The restorative nature of sleep ensures that even minor sleep deficits can have cumulative effects on health.
22
Q
Identify the key brain regions and processes responsible for Encoding
A
The initial stage where sensory information is registered and processed into a short-term memory trace, heavily involving the hippocampus.
23
Q
Identify the key brain regions and processes responsible for Synaptic Consolidation?
A
Strengthening of synaptic connections in the hippocampus that temporarily store the new memory.
24
Q
Identify the key brain regions and processes responsible for Systems Consolidation
A
Over time, memories become redistributed and integrated into the neocortex, diminishing the reliance on the hippocampus.
The interplay between cortical inputs and hippocampal circuits (e.g., place cells and grid cells) facilitates a replay of the experience during sleep, particularly during SWS, which reinforces and transfers the memory trace to long-term storage.
25
Detail how diffuse neuromodulators such as acetylcholine, influence sleep and arousal states.
High during wakefulness and REM, low during SWS; contributes to cortical activation.
26
Detail how diffuse neuromodulators such as norepinephrine and serotonin influence sleep and arousal states.
High during wakefulness; their reduction during sleep permits the transition to slower, synchronized rhythms.
27
Detail how diffuse neuromodulators such as histamine influence sleep and arousal states.
Follows a similar pattern as norepinephrine and serotonin: High during wakefulness; their reduction during sleep permits the transition to slower, synchronized rhythms.
28
Detail how diffuse neuromodulators such as orexin influence sleep and arousal states.
Maintains wakefulness by stabilizing the sleep/wake flip-flop circuit. These systems modulate the firing modes of thalamocortical neurons, transitioning them from burst-firing (seen in SWS) to single-spiking modes (characteristic of wakefulness), thereby influencing overall brain state.
29
Describe the neural “flip-flop” circuit interactions that enforce mutually exclusive sleep and wake states
The flip-flop circuit consists of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO) and wake-promoting regions (e.g., basal forebrain) that mutually inhibit each other. This reciprocal inhibition ensures rapid transitions between sleep and wakefulness, avoiding intermediate states.
30
Describe the role of orexin in preventing unstable transitions in the neural “flip-flop” circuit
Orexin neurons in the lateral hypothalamus further stabilize the circuit by reinforcing wakefulness and counteracting sudden switches to sleep.
Dysfunction in this system, as seen in narcolepsy (where orexin neurons are lost), leads to unstable sleep/wake transitions and the intrusion of REM sleep features during wakefulness.
31
Summarize how the glymphatic system operates to clear metabolic waste from the brain and why its function is enhanced during sleep.
The glymphatic system facilitates the clearance of waste products by propelling cerebrospinal fluid (CSF) through the brain’s interstitial spaces. During sleep, the interstitial space increases by more than 60%, allowing for enhanced convective fluxes that clear protein aggregates (e.g., amyloid-β) and other metabolic byproducts. This process is supported by the polarized distribution of aquaporin-4 (AQP4) water channels on astrocytic endfeet, and the proper functioning of perivascular pathways.
32
Impaired glymphatic clearance has been linked to neurodegenerative conditions such as ?
Alzheimer’s disease
33
Infants and young children exhibit high amounts of ____ sleep and consolidated sleep patterns.
REM,
34
As individuals age, total sleep time declines, _____ decreases, and sleep becomes more fragmented with frequent awakenings.
stage 3 (deep) sleep
35
_______ is characterized by a loss of orexin neurons, leading to abrupt transitions into REM sleep, cataplexy (sudden loss of muscle tone), and sleep paralysis.
Narcolepsy
36
______: occurs when the inhibitory circuits (e.g., within the sublaterodorsal tegmental nucleus or ventromedial medulla) that normally enforce muscle atonia during REM sleep become dysfunctional, resulting in the enactment of dreams.
REM Sleep Behavior Disorder (RBD)
37
Describe how the properties of pyramidal cells—including their geometry, synaptic inputs, and dendritic currents—contribute to the EEG signal.
Pyramidal neurons are arranged in parallel and have long apical dendrites that extend toward the cortical surface. When excitatory synapses release glutamate onto the dendrites, cation channels open, allowing positive ions to flow into the cell. This produces a local intracellular positivity and extracellular negativity near the synapse.
38
Discuss how interactions between thalamic neurons and the reticular nucleus give rise to sleep spindles and other rhythmic patterns in EEG recordings.
Thalamocortical oscillators rely on excitatory thalamocortical neurons and inhibitory neurons. The intrinsic properties of thalamic neurons, such as the activation of low-threshold T-type calcium channels, allow them to generate burst firing when hyperpolarized. This burst firing, + inhibitory feedback from reticular cells, produces rhythmic oscillations known as sleep spindles (brief 12–14 Hz waves). These oscillations help organize the cortex into a state conducive to memory consolidation and synchronized activity during sleep.
39
Contrast the two models of oscillatory generation (two-neuron oscillator vs. one-neuron oscillator)
In a two-neuron oscillator, an excitatory (E) neuron and an inhibitory (I) neuron interact reciprocally. With constant excitatory drive to the E cell, activity alternates between excitation and inhibition, producing a rhythmic pattern.
In a one-neuron oscillator, particularly seen in some thalamic cells during sleep, the neuron itself has intrinsic properties (mediated by specific ion channels) that allow it to fire rhythmically in bursts even without rhythmic external input.
40
Explain the roles of the two models of oscillatory generation in producing rhythmic brain activity.
Both mechanisms contribute to the rhythmic patterns observed in the EEG, with the two-neuron oscillator emphasizing network interactions and the one-neuron oscillator highlighting intrinsic cellular properties.
41
Explain how synchronized activity between the hippocampus and neocortex during sleep supports the consolidation of memories.
Memory consolidation involves the transfer of information from a temporary hippocampal --> permanent neocortical sites during SWS. Slow oscillations from neocortex provide a timing signal for the reactivation of hippocampal memory traces as ripples. This facilitates synaptic plasticity in the neocortex, thereby reinforcing long-term memory storage.
42
Describe how alterations in neuromodulator levels (e.g., acetylcholine, norepinephrine, histamine) influence whether thalamic neurons exhibit burst-firing or tonic spiking.
During deep sleep, lower levels of neuromodulators allow thalamic neurons to remain hyperpolarized, favoring intrinsic burst-firing modes that generate slow, high-amplitude EEG waves.
As these neuromodulators increase during transitions to wakefulness or REM sleep, thalamic neurons depolarize, shifting to a tonic, single-spiking mode. This transition results in a desynchronized EEG with lower amplitude, characteristic of active or alert brain states.
43
Describe how brainstem circuits enforce muscle atonia during REM sleep
During REM sleep, muscle atonia is maintained by a coordinated circuit involving the sublaterodorsal nucleus (SLD) and the ventromedial medulla (VMM). The SLD sends excitatory signals to inhibitory interneurons in the spinal cord, while the VMM further suppresses motor neuron activity.
44
Describe what happens when these circuits that enforce muscle atonia during REM sleep are compromised.
This dual inhibition prevents motor output, ensuring that dreams are not physically enacted. In REM sleep behavior disorder (RBD), degeneration or dysfunction within these circuits leads to a failure of atonia, resulting in the physical enactment of dream content. Patients with RBD may display complex motor behaviors during REM sleep, potentially causing injury to themselves or their bed partners.
45
Define pain
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It comprises two main components.
46
________: This aspect includes the location, intensity, and quality of the noxious stimulus. It is primarily processed in brain regions such as the primary (S1) and secondary (S2) somatosensory cortices as well as the posterior insula.
Sensory–discriminative
47
_________: This aspect encompasses the emotional response, including feelings of unpleasantness, fear, and anxiety, along with associated autonomic responses. It is processed in regions like the dorsal anterior cingulate cortex (dACC) and anterior insula (AI).
Affective–motivational
48
Explain how patients with lesions in certain brain regions can experience pain without its accompanying emotional distress.
Asymbolia: a condition in which individuals perceive noxious stimuli as painful and can identify characteristics like intensity and location, but they do not experience the usual emotional distress or suffering. This dissociation occurs when there is damage to regions such as the anterior cingulate cortex or insular cortex—areas that normally mediate the affective component of pain.
49
Discuss how social rejection and exclusion activate neural circuits similar to those used in processing physical pain.
Social pain refers to the distressing experience associated with social rejection or loss of social connection. Neuroimaging studies show that social exclusion activates the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), the same areas that process the affective dimension of physical pain. This neural overlap explains why interventions like opiates or even placebo treatments can reduce distress in both physical and social pain contexts
50
Define nociception and explain how nociceptors and free nerve endings detect noxious stimuli
Nociception: sensory process of encoding and processing harmful stimuli that may result in tissue damage.
Nociceptors: typically unspecialized free nerve endings; detect physical stimuli (mechanical, thermal, or chemical stimuli) --> electrical signals via sensory transduction using receptor potentials --> that initiate action potentials along dedicated labeled lines to the brain
51
In the Sleep/Waking Flip-Flop, there is mutual inhibition between which two regions?
The SWS-on region (vIPOA) and the Waking-on region (arousal system)
52
In the Sleep/Waking Flip-Flop, the arousal system leads to what?
The neuromodulators
53
In the Sleep/Waking Flip-Flop, the SWS-on region (vIPOA) leads to what?
LH orexinergic neurons and the REM-off (vIPAG)
54
LH orexinergic neurons lead to what?
Arousal system and REM-off (vIPAG)
55
In the REM Sleep Flip-Flop, there is mutual inhibition between which two regions?
REM-off (vIPAG) and REM-on (SLD)
56
What feeds into the REM-on (SLD)?
emotional stimuli, which stimulates amygdala
57
What is the SLD in the REM-on?
Sublaterodorsal nucleus
58
Describe how energy from a noxious stimulus is converted into neural signals and communicated via distinct pathways.
Receptor cells convert a stimulus (such as heat or pressure) --> change in the electrical potential.
Each type of receptor (stretch, vibration, or pain) sends information along specific neural pathways known as labeled lines. These pathways ensure distinction of a stimuli are preserved and transmitted accurately to the brain.
59
Identify the different transient receptor potential (TRP) channels:
_______: Activated by moderate heat and capsaicin, it signals a burning sensation.
TRPV1 (vanilloid receptor 1)
60
Identify the different transient receptor potential (TRP) channels:
______: Responds to high temperatures, transmitting signals of sudden, sharp pain.
TRPM3
61
Identify the different transient receptor potential (TRP) channels:
_____: Activated by cool temperatures or menthol, conveying a sensation of cooling.
TRPM8
62
Each of these TRP receptors is associated with specific types of nerve fibers:
___ fibers for TRPM3
________ for TRPV1 and TRPM8
Aδ, Unmyelinated C fibers
63
Explain how peripheral sensitization increases the responsiveness of nociceptors following tissue injury
Peripheral sensitization occurs when the thresholds for nociceptor activation are lowered by local inflammatory mediators (often described as an “inflammatory soup”) that include bradykinin, prostaglandins, histamine, and cytokines. These substances, released by mast cells and macrophages, activate signaling cascades (involving protein kinases such as PKA and PKC) that modify receptor channels like TRPV1. The result is an enhanced response to painful stimuli (hyperalgesia) or pain elicited by normally non-painful stimuli (allodynia)
64
Describe the mechanisms by which nociceptors contribute to inflammation and amplify pain signals through antidromic signaling
When action potentials in nociceptors not only transmit signals to the central nervous system but also travel antidromically (backward) along peripheral branches.
This causes release of neuropeptides such as substance P and calcitonin gene–related peptide (CGRP) from the nerve terminals.
Substance P can trigger mast cell degranulation (releasing histamine), and CGRP acts as a potent vasodilator.
Antidromic impulses can amplify local inflammation and pain by spreading the release of these substances to neighboring tissue
65
Outline the anatomical routes through which pain signals travel from peripheral nociceptors to the brain:
Anterolateral (Spinothalamic) System
Nociceptive fibers (both myelinated Aδ and unmyelinated C fibers) synapse in the dorsal horn of the spinal cord. Second-order neurons then cross the midline and ascend in the contralateral anterolateral column to reach the thalamus, which relays the information to various cortical regions (including the somatosensory and cingulate cortices).
66
Outline the anatomical routes through which pain signals travel from peripheral nociceptors to the brain:
Dorsal Column Pathway
This pathway is specialized for mechanosensory information and ascends ipsilaterally before crossing over at the level of the medulla
67
The anatomical organization of these pain pathways explains phenomena such as referred pain, where ?
visceral pain is misinterpreted as originating from somatic regions due to convergent inputs in the dorsal horn
68
Explain why and how pain from visceral organs can be experienced in somatic regions
Referred pain occurs because visceral nociceptive afferents and somatic afferents converge onto the same projection neurons in the dorsal horn of the spinal cord. When the brain receives convergent signals, it may misattribute the source of the pain. For example, pain from a myocardial infarction is often felt as deep chest pain or radiates to the left arm due to the overlap in neural pathways
69
Understand the contribution of voltage-gated sodium channels (e.g., Nav1.7 and Nav1.8) to the initiation and propagation of nociceptive signals
Pain-specific sodium channels are crucial for the generation and conduction of action potentials in nociceptive fibers. Nav1.7 channels are important for initiating action potentials at the nociceptor terminals, while Nav1.8 channels sustain the propagation of these signals along the axon. Genetic mutations that affect these channels can lead to altered pain perception—loss-of-function mutations in Nav1.7 may result in insensitivity to pain, whereas gain-of-function mutations can lead to chronic pain conditions
70
Explain how natural selection can influence pain perception, using the example of grasshopper mice and bark scorpion venom
In an evolutionary adaptation, grasshopper mice have developed a mutation in the Nav1.8 channel that allows bark scorpion venom to block this channel. While the venom activates Nav1.7 (which typically generates pain), its simultaneous inhibition of Nav1.8 in grasshopper mice prevents the propagation of pain signals, conferring resistance to the venom’s painful effects.
71
Describe how descending pathways and endogenous opioid systems regulate the transmission of pain signals at the spinal level
The central modulation of pain involves descending monoaminergic pathways that originate in brain regions such as the periaqueductal gray (PAG) and the nucleus raphe magnus. These pathways—using neurotransmitters—project to the dorsal horn of the spinal cord where they inhibit nociceptive projection neurons directly or via interneurons (often releasing enkephalins). This inhibition reduces the duration and amplitude of postsynaptic potentials, thereby decreasing pain perception. Endogenous opioids (endorphins, enkephalins, dynorphins) also bind to opioid receptors distributed in the brain, brainstem, spinal cord, and peripheral tissues to further dampen pain signals
72
Analyze how the placebo effect can modulate pain perception through contextual, cognitive, and neurochemical mechanisms
The placebo effect is a physiological response where an inert treatment produces real pain relief. This effect is mediated by both external context and internal factors. Placebo analgesia is associated with increased endogenous opioid and dopamine neurotransmission in brain regions implicated in pain regulation. This leads to decreased activity in pain-processing areas such as the dorsal anterior cingulate cortex (dACC), thereby reducing the subjective experience of pain
73
Describe the anatomical location of the basal ganglia
The basal ganglia are deep subcortical structures that lie within the cerebral hemispheres and extend into the anterior part of the midbrain (including the substantia nigra). They are positioned lateral to the thalamus.
74
List the primary functions of the basal ganglia in motor control (4)
o do not directly initiate movement, they modulate motor circuits to:
o Regulate involuntary movements
o Tune and refine voluntary movements
o Maintain posture
75
Identify non-motor functions in which the basal ganglia are involved
In addition to motor control, working memory, motivation, decision-making, and other cognitive processes
77
Name the major neuroanatomical components of the basal ganglia:
______: Consisting of the globus pallidus (divided into external and internal segments) and the substantia nigra pars reticulata (serving as output structures)
Pallidum
78
Name the major neuroanatomical components of the basal ganglia:
_______: Comprising the caudate nucleus and putamen (serving as the input zone)
Striatum
78
Name the major neuroanatomical components of the basal ganglia:
_________: Works in concert with the pallidal structures
Subthalamic Nucleus
79
Compare the location between the striatum and the pallidum
Striatum: Input zone
Pallidum: Output zone
80
Compare the neuronal type between the striatum and the pallidum
Striatum: Predominantly medium spiny neurons (MSNs) subdivided into D1-MSNs and D2-MSNs
Pallidum: Large inhibitory GABAergic projection neurons (with additional dopaminergic neurons in parts of the substantia nigra)
81
Compare the physiology between the striatum and the pallidum
Striatum: Low spontaneous activity; requires strong excitation
Pallidum: High spontaneous activity; continuously inhibits target structures
82
Compare the function between the striatum and the pallidum
Striatum: Processes motor and cognitive inputs
Pallidum: Regulates movement by providing inhibitory outputs to the thalamus and brainstem
83
Explain the structure and function of medium spiny neurons (MSNs) in the striatum
MSNs constitute approximately 75% of the striatal neurons and feature large dendritic trees to integrate inputs from the cortex, thalamus, and brainstem. They are GABAergic output neurons that play a central role in processing motor and cognitive signals and serve as the main conduits for direct and indirect pathways
84
Outline the sources of input received by medium spiny neurons (4)
The cerebral cortex (corticostriatal pathway)
Local circuit interneurons within the striatum
The thalamus (via the thalamostriatal pathway)
Various nuclei in the brainstem
85
Describe the role of dopamine in modulating MSN activity and the differences between D1 and D2 receptor-mediated responses
_________: Activation increases cAMP, enhancing excitatory cortical input; associated with the direct pathway that facilitates movement.
D1 Receptors (D1R)
86
Describe the role of dopamine in modulating MSN activity and the differences between D1 and D2 receptor-mediated responses
________: Activation decreases cAMP, suppressing cortical excitation; associated with the indirect pathway that inhibits competing movements
D2 Receptors (D2R)
87
Explain the function of inward-rectifier K⁺ channels in medium spiny neurons
Inward-rectifier K⁺ channels in MSNs remain open at resting potential, which stabilizes the neuronal membrane and makes spontaneous firing unlikely. When a strong excitatory input depolarizes the neuron, these channels close, increasing the neuron's excitability and allowing action potentials to be generated
88
Differentiate the route of the direct and indirect pathways of the basal ganglia
Direct Pathway: MSNs in the striatum project directly to the internal segment of the glob-us pallidus (GPi).
Indirect Pathway: MSNs project to the external segment of the globus pallidus (GPe), which in turn influences the subthalamic nucleus; this then excites the GPi and substantia nigra pars reticulata, enhancing thalamic inhibition.
89
Differentiate the function of the direct and indirect pathways of the basal ganglia
Direct Pathway: initiation of a specific motor program.
Indirect Pathway: Suppresses competing or unwanted motor programs.
90
Explain the concept of disinhibition in the context of the direct pathway
In the direct pathway, the activation of MSNs inhibits the GPi, which normally exerts tonic inhibitory control over thalamic neurons. This inhibition of the GPi (disinhibition of the thalamus) allows the thalamus to relay motor commands to the cortex, thereby initiating movement
91
Describe the role of the indirect pathway in regulating movement
MSN activation --> GPe --> ↓ inhibition of the subthalamic nucleus --> ↑ excitatory input to the GPi and substantia nigra pars reticulata --> ↑ inhibition of thalamic relay neurons --> suppress unwanted or competing movements
92
Identify the major input pathways to the basal ganglia and their origins:
Corticostriatal Pathway
The caudate receives input from multimodal association cortices and eye-movement control regions; the putamen receives input from somatosensory, visual, motor, and auditory areas.
93
Identify the major input pathways to the basal ganglia and their origins
Thalamostriatal Pathway
Contributes additional excitatory signals to the striatum.
94
Identify the major input pathways to the basal ganglia and their origins
Dopaminergic Pathway
Arises from the substantia nigra pars compacta and modulates striatal neuron activity.
95
Identify the major output pathways from the basal ganglia and their targets
From the Striatum
The direct pathway projects to the internal segment of the globus pallidus (GPi).
The indirect pathway projects to the external segment of the globus pallidus (GPe) and the substantia nigra pars reticulata.
96
Identify the major output pathways from the basal ganglia and their targets
From the Globus Pallidus
Outputs target the ventral anterior and ventral lateral nuclei of the dorsal thalamus, which then communicate with motor areas of the cortex.
97
Identify the major output pathways from the basal ganglia and their targets
From the Substantia Nigra Pars Reticulata
Outputs project directly to the superior colliculus, influencing head and eye movements.
98
Explain how the basal ganglia contribute to movement control using saccadic eye movements as an example
Before a saccadic eye movement, MSNs in the caudate are activated by cortical signals, which then inhibit the substantia nigra pars reticulata. This reduction in tonic inhibition (disinhibition) of the superior colliculus allows its upper motor neurons to fire a burst of action potentials, thereby initiating the saccadic eye movement. The substantia nigra pars reticulata thus acts as a "gate" controlling movement
99
Discuss the effects of basal ganglia damage in hypokinetic disorders, such as Parkinson’s disease
In Parkinson’s disease, the loss of dopaminergic neurons in the substantia nigra pars compacta leads to reduced dopamine levels. This imbalance results in an overactive indirect pathway, which increases the inhibition of thalamic neurons. Clinically, this manifests as bradykinesia (slowed movement), resting tremor, rigidity, and postural instability. Treatments include L-DOPA therapy and Deep Brain Stimulation (DBS).
100
Discuss the effects of basal ganglia damage in hyperkinetic disorders, such as Huntington’s disease
In Huntington’s disease, degeneration of medium spiny neurons, particularly those in the indirect pathway, leads to a loss of inhibitory control. The result is overactivation of thalamic neurons and the appearance of involuntary, erratic movements (chorea), along with cognitive decline and emotional disturbances. Treatment typically focuses on symptomatic management with dopamine antagonists
101
Explain how animal models are used to study hyperkinesia related to basal ganglia dysfunction
Animal models often involve the injection of substances like muscimol—a GABA agonist—into the substantia nigra pars reticulata. This reduces its tonic inhibitory output, leading to disinhibition of the superior colliculus and resulting in involuntary saccadic eye movements.
102
Describe the principles and clinical application of deep brain stimulation (DBS) in treating movement disorders
Implanting surgically placed electrodes in specific brain regions (commonly the internal segment of the globus pallidus or the subthalamic nucleus).
Fine-tuning stimulation parameters post-surgery to optimize motor control.
DBS modulates abnormal neuronal activity and can improve symptoms in both hypokinetic and hyperkinetic movement disorders.
103
Explain the anatomical location, structural features, and interconnections of the primary motor cortex (M1)
The primary motor cortex (M1) is located in the most dorsal portion of the frontal lobes, immediately anterior to the central sulcus, forming the precentral gyrus. This location is ideal for rapid integration of sensory information from adjacent regions.
o M1 is not an isolated region; it constantly communicates with the basal ganglia, cerebellum, and other cortical areas. This network ensures that motor commands are executed in a coordinated, intentional, and precise manner. The M1 directs muscle contractions needed to perform movements.
104
Describe the map of motor control known as the homunculus and discuss how it reflects the functional demands of different body parts.
Researchers have mapped the primary motor cortex to reveal a somatotopic organization—each region corresponds to control over specific parts of the body. This map, known as the homunculus, shows disproportionate representations: body parts requiring fine motor control (like the hands and face) are overrepresented (appearing larger), while areas with less precise movements (such as the legs and torso) are smaller.
105
Outline Wilder Penfield’s contributions to our understanding of the motor cortex and its somatotopic organization.
Wilder Penfield, a Canadian neurosurgeon, used electrical stimulation on the cortex of patients undergoing epilepsy surgery. His goal was to remove as little brain tissue as possible while targeting the area initiating seizures.
o Penfield discovered that stimulating different parts of the precentral gyrus produced movements in specific body parts. His work established the concept of a central map of the body (the motor homunculus) and demonstrated that the cortex is organized in a somatotopic fashion. This laid the groundwork for modern neuroscience’s understanding of motor control.
106
Discuss how individual cortical neurons can influence multiple muscle groups and the significance of intracortical microstimulation:
Single Neuron Influence
A single spike from a pyramidal tract neuron in M1 can trigger a measurable response in a thumb muscle, demonstrating a fixed latency relationship. This observation indicates that one cortical neuron can impact several motor neuron pools controlling different muscles.
107
Discuss how individual cortical neurons can influence multiple muscle groups and the significance of intracortical microstimulation.
Intracortical Microstimulation
Using microelectrodes, scientists can deliver very precise currents and record activity from individual neurons. This technique, which uses currents an order of magnitude lower than Penfield’s, has revealed that stimulating one neuron can activate multiple muscles. The results suggest that the motor cortex organizes movements not by controlling individual muscles but by coordinating groups of muscles to achieve a goal-directed movement.
108
Describe the Experimental Setup for Recording Neuronal Activity During a Visually Guided Reaching Task
Researchers designed an experiment using a monkey that begins at a central position and uses a joystick to reach toward a cue indicated by a green light. The task is structured so that the monkey must reach toward one of eight possible positions (each corresponding to a specific direction). After completing the movement toward the cue, the monkey returns to the center. Throughout this task, the activity of individual cortical neurons is recorded using microelectrodes, capturing the precise timing and rate of neuronal firing relative to movement onset.
109
Explain the Concept of Directional Tuning in Individual Motor Cortex Neurons
Directional tuning refers to the phenomenon where the firing rate of an individual motor cortex neuron varies depending on the direction of movement. In the experiment:
Some neurons exhibit increased firing when the monkey moves in one direction (for example, around 135°). For other directions (such as 45° and 315°), these neurons show decreased activity.
o This variation indicates that each neuron “prefers” a particular direction of movement, contributing most robustly when that movement direction is executed.
110
Define a Neuron’s “Preferred Direction” and Illustrate How It Is Represented as a Vector
Preferred Direction: Each neuron in the motor cortex has a specific movement direction where its firing rate reaches a maximum. This is known as the neuron’s “preferred direction.”
Vector Representation: The preferred direction can be visualized as a vector where: The direction of the vector represents the angle (or movement direction) at which the neuron fires most strongly (e.g., 135° or an equivalent clock position such as 11 o’clock); The length of the vector reflects the strength (or firing rate) of the neuronal response in that direction.
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Explain the Concept of Population Coding and How It Predicts Movement Direction
Although each neuron is broadly tuned and contributes to a range of movement directions, every neuron “casts a vote” in favor of its preferred direction based on its firing rate. By plotting each neuron’s directional vector and averaging them, researchers derived a single “population vector.”
Population coding is the process by which the collective activity of many neurons, each with its own preferred direction and degree of activation, is integrated to produce a precise control signal for movement. It’s similar to how multiple sensory inputs can be averaged to form a coherent percept (as in olfaction).
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Explain how the insights from motor cortex studies, such as population coding and neural plasticity, have led to advances in clinical therapies and brain–machine interfaces:
Brain–Machine Interfaces (BMIs)
The concept of population coding is used in BMIs. For example, in clinical settings, microelectrode arrays implanted in the motor cortex of tetraplegic patients record neural signals. Algorithms translate these signals into movement commands for robotic prosthetic arms, enabling patients to manipulate objects in a three-dimensional space solely through thought.
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Explain how the insights from motor cortex studies, such as population coding and neural plasticity, have led to advances in clinical therapies and brain–machine interfaces:
Neurorehabilitation and Plasticity
The motor cortex exhibits plasticity—its ability to remap and reorganize in response to learning or after injury. Understanding this plasticity is essential for developing rehabilitation strategies that help restore lost functions following strokes or injuries by promoting cortical reorganization and motor learning
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Distinguish between the primary motor cortex and nonprimary motor areas (premotor cortex and supplementary motor area) in terms of their contributions to movement initiation and planning:
Primary Motor Cortex (M1)
M1 is primarily involved in executing movements in response to external cues. It directly controls muscle contractions and forms the final output stage of motor planning.
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Distinguish between the primary motor cortex and nonprimary motor areas (premotor cortex and supplementary motor area) in terms of their contributions to movement initiation and planning:
Nonprimary Motor Areas - Premotor Cortex
Located anterior to M1, it is involved in the planning and selection of movements, particularly those guided by external cues. It shows increased neuronal activity during the preparation phases (ready and set) before movement execution.
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Distinguish between the primary motor cortex and nonprimary motor areas (premotor cortex and supplementary motor area) in terms of their contributions to movement initiation and planning:
Nonprimary Motor Areas - Supplementary Motor Area (SMA)
Found on the medial surface of the hemispheres, the SMA is critical for planning and coordinating complex, internally generated movement sequences. Lesions in the SMA can reduce spontaneous movement and disrupt well-learned behavioral sequences, highlighting its role in self-initiated actions.
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Differentiate Between Primary and Nonprimary Motor Cortex Functions:
Primary Motor Cortex (M1)
Responsible for direct execution of movements by controlling muscle contractions.
Driven largely by external cues—such as performing a motor sequence in response to sensory information or instructions.
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Differentiate Between Primary and Nonprimary Motor Cortex Functions:
Nonprimary Motor Areas (Premotor Cortex & SMA)
Involved in planning, selecting, and sequencing movements, especially complex or internally generated ones.
They modulate the activity of M1 through extensive intercortical interactions.
Their contributions are critical for actions that are self-initiated rather than prompted by external stimuli.
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Describe the Neuronal Discharge Patterns in the Premotor Area During Movement Preparation. Experimental Paradigm (“Ready, Set, Go”): In studies with monkeys, researchers record the activity of neurons in the premotor area (PMA) during a task involving a panel of lights.
Ready Phase:
The monkey waits for an instruction cue indicating which movement is required.
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Describe the Neuronal Discharge Patterns in the Premotor Area During Movement Preparation. Experimental Paradigm (“Ready, Set, Go”): In studies with monkeys, researchers record the activity of neurons in the premotor area (PMA) during a task involving a panel of lights.
Set Phase
A specific instruction (e.g., a red light) prompts the premotor neuron to discharge, indicating the preparation of movement.
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Describe the Neuronal Discharge Patterns in the Premotor Area During Movement Preparation. Experimental Paradigm (“Ready, Set, Go”): In studies with monkeys, researchers record the activity of neurons in the premotor area (PMA) during a task involving a panel of lights.
Go Phase:
A trigger stimulus (blue light) signals the monkey to move, and shortly after the movement starts, the neuron ceases firing.
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Describe the Neuronal Discharge Patterns in the Premotor Area During Movement Preparation. Experimental Paradigm
These discharge patterns indicate that PMA neurons are actively involved in movement preparation and timing, contributing to the initiation of the movement plan before execution
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Explain the Role of the Supplementary Motor Area (SMA) in Complex Behavioral Sequences
The SMA is key for coordinating sequences of movements, particularly those that are internally generated (e.g., performing a well-practiced sequence like unlocking a door).
Studies show that when a monkey performs a sequence of movements (such as a pulling action followed by a pushing action), specific SMA neurons fire selectively during certain parts of the sequence
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Explain the Role of the Supplementary Motor Area (SMA) in Complex and Internally Generated Movements
o Lesions or strokes affecting the SMA can result in a reduction in spontaneous or self-initiated movements.
o Individuals with SMA damage may retain the ability to perform movements in response to external cues, but they experience difficulty with tasks that require internally generated motor sequences.
o The SMA receives input from the basal ganglia and helps modulate M1 activity to ensure that complex sequences are executed smoothly.
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Discuss the Integration of Nonprimary Motor Areas in Motor Planning
Both the premotor cortex and SMA work in concert with the primary motor cortex to plan and refine movements.
Their activity is essential for preparing the motor system, particularly for actions that require internal planning and sequencing.
These nonprimary areas help bridge the gap between the conceptualization of an action and its execution by M1.
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Discuss the Integration of Nonprimary Motor Areas in Motor Planning and Their Clinical Implications
Understanding these interactions is crucial for designing rehabilitation protocols for patients with motor impairments (e.g., post-stroke). Therapeutic strategies may focus on enhancing the plasticity and function of nonprimary motor areas to compensate for damaged M1 regions. In conditions where internally generated movements are affected (as seen with SMA lesions), targeted interventions could help restore the capacity for self-initiated motor actions.
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Define Mirror Neurons
Mirror neurons are a specialized class of neurons that are active both when an individual executes a specific movement and when the same movement is observed being performed by another. This dual activation suggests a neural mechanism for understanding actions through internal simulation.
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Identify the Anatomical Location of Mirror Neurons
Mirror neurons are predominantly found in the ventral portion of the premotor cortex, particularly in area F5. This region is critical for planning and executing movements and, in the context of mirror neurons, for linking observed actions with internal motor representations.
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Describe the Firing Properties of Mirror Neurons During Action Execution and Observation
o Mirror neurons in area F5 fire when a monkey (or human) is about to perform a reaching action—for example, reaching for a box. They also fire when the individual observes another (such as a human experimenter) performing the same reaching action.
o Importantly, these neurons fire most robustly when the observed action is goal-directed (e.g., reaching for a box to grasp it). In contrast, when the action lacks an obvious goal—such as reaching without an object—the firing rate is much less vigorous. This modulation suggests that mirror neurons are tuned not only to the movement itself but also to the intention behind the movement.
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Explain How Mirror Neurons Discriminate Between Goal-Directed and Non-Goal-Directed Actions
o The response of mirror neurons is significantly stronger when the observed movement has a clear purpose or goal. For example, when a monkey or human reaches for a box (an action with an immediate, identifiable target), the mirror neuron response is markedly higher compared to a reach without any associated object.
o This ability to discriminate indicates that mirror neurons contribute to the neural coding of action intentions. They provide a rapid, automatic mechanism by which the brain infers the purpose behind an observed movement, aiding in immediate and unconscious understanding of others’ behaviors.
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Discuss the Role of Mirror Neurons in Understanding Others’ Intentions
o Understanding intentions is central to human social behavior. Mirror neurons allow an individual to simulate and internally represent the observed actions of others, which facilitates the rapid comprehension of another’s goals and intentions without the need for conscious reasoning.
o As social beings, this mechanism provides a survival advantage by enabling quick reactions to the actions of others, whether in cooperative scenarios or in recognizing potential threats. The immediate comprehension of others’ intentions helps coordinate social interactions and can lead to better prediction of behavior.
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Evaluate Experimental Evidence Demonstrating Mirror Neuron Function in Intention Recognition
Activation in mirror neuron populations within the premotor cortex was strongest in scenes that clearly signaled a goal (such as drinking). This indicates that mirror neurons are more responsive to actions with clear, intentional outcomes. Furthermore, mirror neurons distinguished between different intentions by responding more intensely to actions fulfilling a basic need (drinking) compared to those with a secondary, culturally influenced purpose (cleaning).
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Assess the Impact of Disrupting Mirror Neuron Function on Social Cognition
Transcranial Stimulation Studies: Experiments involving transcranial stimulation—which disrupts normal cortical function—have shown that when mirror neuron activity is interfered with, subjects have difficulty inferring the intentions behind observed actions. This disruption reinforces the idea that mirror neurons are essential for normal social cognitive processes, such as understanding what another person is about to do or inferring their goals.
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Assess the Impact of Disrupting Mirror Neuron Function on Autism
Clinical Implications: Such findings are especially relevant when considering social cognitive deficits observed in conditions like autism. Underactivation or dysfunction in mirror neuron regions, such as the pars opercularis, may contribute to challenges in imitation, empathy, and the interpretation of others’ intentions, leading to broader social impairments.
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Describe how motor learning leads to cortical remapping and discuss its significance for both skill acquisition and recovery from injury.
o Motor Learning and Plasticity: As new motor skills are acquired, the motor cortex undergoes reorganization—a process known as cortical remapping. This plasticity allows previously unengaged or underutilized regions to take on new roles, ensuring efficient execution of learned movements.
o After an injury, such as a stroke that affects muscle movement, this inherent plasticity can be harnessed through rehabilitation. By engaging in specific motor tasks, the brain can reassign and reinforce pathways that restore lost functions, underscoring the importance of motor learning in neurorehabilitation.
