Introduction to neuroimaging 25-26.pdf

# Peripheral measures of physiological activity Peripheral measures of physiological activity offer indirect insights into cognitive and affective processes by reflecting autonomic and somatic nervous system activation [1](#page=1) [5](#page=5). ## 1. Peripheral measures of physiological activity ### 1.1 Skin conductance Skin conductance, also known as electrodermal activity (EDA), primarily reflects sympathetic nervous system (SNS) activity associated with the "fight or flight" response. Arousal stimulates sweat glands, increasing the skin's electrical conductivity. This measure is largely interpreted as an index of arousal intensity during affective or cognitive processing, irrespective of valence (positive vs. negative). Higher arousal generally leads to higher skin conductance [1](#page=1). **Method:** Two electrodes are typically attached to the palm side of the fingers or the palm of the non-dominant hand, as the dominant hand is often used for tasks. A very small voltage is applied, and the current passed is measured as conductivity. More arousal results in increased EDA. Typical units are microsiemens ($\mu$S) or microohms ($\mu$mho). The speed of current flow between electrodes indicates higher conductivity [1](#page=1). **Different measures:** * **Skin Conductance Level (SCL):** This is a tonic, slow-changing measure reflecting baseline arousal over time. It shows significant inter-individual differences, and while absolute values may be less meaningful, they are useful for comparing different conditions across time blocks [2](#page=2). * **Non-Specific Skin Conductance Response (NS-SCR):** These are spontaneous, phasic changes in electrical conductivity that are not directly stimulus-locked. They can reflect general arousal or spontaneous reactions unrelated to the task [2](#page=2). * **Event-Related Skin Conductance Response (ER-SCR):** This is a phasic response to a specific event or stimulus, with a latency of 1-3 seconds after stimulus presentation. ER-SCR is considered the most interesting measure for experimental manipulation as it shows how the body reacts to specific stimuli such as images, sounds, or decisions [2](#page=2). > **Example 1: Affective picture processing (Öhman & Soares - 1994)** > Skin conductance is frequently used in fear conditioning research to quantify the intensity of a person's fear response to conditioned stimuli. For instance, if an individual fears snakes but not spiders, their skin conductance response will be higher when viewing a snake compared to a spider, indicating selectivity for the fear-inducing stimulus. SCR can thus reveal individual differences in emotional reactivity. A control group would show lower responses overall [2](#page=2). > **Example 2: Stop-signal task (Zhang et al. - 2012)** > This task assesses response inhibition. Participants see circles requiring a button press, followed by an 'X' signal to inhibit the press. In mixed GO and Stop trials, ER-SCR is lowest for GO trials, intermediate for successful Stop trials (SS), and highest for failed Stop trials (SE). This suggests increased arousal, particularly when inhibition fails [2](#page=2). ### 1.2 Pupillometry Pupil size is influenced by luminance (light levels) but also reflects fluctuations in the autonomic nervous system, indicating arousal, surprise, mental effort, and adaptation in uncertain environments. Low luminance or SNS stimulation causes pupil dilation, while high luminance or parasympathetic nervous system (PNS) stimulation causes pupil constriction [3](#page=3). **Underlying mechanism:** Pupil dilation is directly linked to the firing rate of neurons in the locus coeruleus, a brainstem region rich in neuroadrenergic neurons. As these neurons fire, pupil dilation follows their pattern [3](#page=3). **Method:** An infrared light source illuminates the eye, and an infrared-sensitive camera captures the contrast between the pupil and the iris. When illuminance is kept constant, changes in pupil size can indicate cognitive processes or mental effort during experimental tasks. It is crucial to ensure no illuminance differences between experimental conditions [3](#page=3). > **Example: Flanker conflict task (Braem et al. - 2015)** > In this task, participants judge a central target while ignoring surrounding flankers, which can be congruent or incongruent with the target. Pupil size is elevated for all incongruent trials and for incorrect trials. The largest pupil response is observed in congruent-incorrect trials, likely due to surprise when an easy trial is performed incorrectly [3](#page=3). **Note:** Pupillometry is distinct from eye-tracking, although they use similar equipment. Eye-tracking is more controlled and relates to behavioral measures like reaction time and accuracy, whereas pupil movement is involuntary [3](#page=3). ### 1.3 Cardiac activity The heart's primary role is oxygen and nutrient transport. It responds significantly to exercise and requires controlled monitoring during cognitive tasks. The cardiac cycle, with an intrinsic rhythm of approximately 105 bpm, is initiated by the sino-atrial node (pacemaker) and conducted through the atrioventricular node. The PNS slows the heart rate, while the SNS speeds it up [3](#page=3). **Main methods and measures:** * **Electrocardiography (ECG):** Measures Heart Rate (HR) and Heart Rate Variability (HRV) [4](#page=4). * **Impedance Cardiography (ICG):** Measures the Pre-Ejection Period (PEP) [4](#page=4). #### 1.3.1 Electrocardiography (ECG) ECG records the heart's electrical activity via surface electrodes, reflecting the production and conduction of action potentials during the cardiac cycle [4](#page=4). **Heart Rate (HR):** HR is based on the RR interval (time between consecutive R-waves in an ECG) and is measured in beats per minute (bpm). It is sensitive to emotional processes influenced by the SNS and PNS. The formula for HR is [4](#page=4): $$ HR = \frac{60}{\text{RR interval in seconds}} $$ Physical activity is the primary influence on HR, but psychological and cognitive factors like stress, emotions, and task load also play a significant role [4](#page=4). > **Example 1: Emotional states (Prkachin et al. - 1999)** > Emotional states typically elevate heart rate, reflecting SNS influence [4](#page=4). > **Example 2: Affective picture processing (Bradley et al. - 2012)** > Heart rate can decrease when orienting attention to emotional pictures, reflecting PNS influence. However, a more common observation is that heart rate increases when emotional events require action or during states of fear, stress, or anger, reflecting SNS influence [4](#page=4). **Heart Rate Variability (HRV):** HRV refers to the changes in time intervals between consecutive heartbeats (RR intervals). It serves as a general measure of PNS influence on the heart. Also termed inter-beat intervals (IBIs), baseline HRV differs between individuals ("trait") and can be influenced by cognitive demand ("state"). Generally, high HRV predicts better cognitive performance [4](#page=4). #### 1.3.2 Impedance Cardiography (ICG) ICG measures the total electrical conductivity of the thorax and its changes over time. A high-frequency current flows between an electrode pair, and changes in impedance are detected by a second pair, producing an impedance pulse wave and the ICG curve [5](#page=5). **Pre-Ejection Period (PEP):** The PEP is the time interval from ventricular electrical stimulation to the opening of the aortic valve, thought to reflect SNS influence on the heart. This measure cannot be derived from ECG alone as it does not involve the aortic valve. The duration of PEP varies individually [5](#page=5). > **Example: Subliminal response priming (Glendolla & Silvestrini - 2013)** > In a letter detection task with primes, PEP was used to assess effort mobilization. Subliminal primes modulated PEP, showing shorter PEP for action versus inaction. Monetary incentives further reduced PEP. Reduced PEP is associated with better task performance, suggesting a more activated state enhances performance [5](#page=5). ### 1.4 Respiration Respiratory activity is measured using a belt around the chest. There is a relationship between respiration and heart rate; faster respiration leads to a faster heart rate. Respiration increases with physical activity but is also influenced by psychological and cognitive factors like stress, emotion, and task load. Both SNS and PNS influence respiration. Respiration can be actively used to modulate autonomic nervous system activity, for instance, slow breathing can activate the PNS [5](#page=5). **Different measures of interest:** * Respiratory rate (most relevant for cognitive neuroscience) [6](#page=6). * Inspiration time [6](#page=6). * Expiration time [6](#page=6). * Inspiration to expiration ratio [6](#page=6). > **Example: Working memory task (Backs & Seljons - 1994)** > In a task involving streams of letters where participants report the frequency of a specific letter, respiration rate was found to increase with memory load and stimulus speed. Faster stimulus presentation leads to faster breathing [6](#page=6). ### 1.5 Muscle activity (Somatic NS) Electromyogram (EMG) measures electrical field changes due to muscle action potentials, providing a connection to the motor cortex. Two electrodes are placed above the muscle of interest, along with a ground electrode. EMG is always recorded from striated muscle, which requires neural stimulation to contract. Muscle activity is detected when the motor cortex is active for that specific muscle [6](#page=6). **Different measures of interest:** * Blink reflex [6](#page=6). * Facial EMG [6](#page=6). * Motor EMG [6](#page=6). #### 1.5.1 Blink reflex The blink reflex, or startle reflex, is measured by surface electrodes placed below the eye, targeting the orbicularis oculi muscle. It can be induced by external stimuli like air puffs, touch, light flashes, or sounds. The speed of the blink is influenced by the autonomic nervous system, integrating autonomic and somatic nervous system functions [6](#page=6). > **Example: Affective sound processing (Bradley & Lang - 2000)** > The blink reflex to a light flash was stronger during unpleasant sounds compared to pleasant sounds. This suggests we are less startled in pleasant surroundings because we perceive less potential danger. This finding correlates with subjective pleasantness ratings [6](#page=6). #### 1.5.2 Facial EMG Facial EMG is measured using surface electrodes placed above different facial muscles, commonly the corrugator (frown) muscle above the eye and the zygomaticus (smile) muscle on the cheek. It is used to assess responses to affective stimuli and during cognitive processing [7](#page=7). > **Example: Simon conflict task (Cannon et al. - 2010)** > In a task requiring categorization of objects with either the left or right hand, where the object's handle location could be compatible or incompatible with the response hand, facial EMG was measured. Compatible trials showed increased activation of smile muscles, indicating a preference for these trials. Incompatible trials showed increased activation of the frown muscle [7](#page=7). #### 1.5.3 Motor EMG Motor EMG is measured by surface electrodes placed above peripheral muscles, passively recording muscle activity beneath the skin. It can be used during cognitive tasks that require manual responses [7](#page=7). > **Example: Simon conflict task (Burle et al. - 2002)** > In a task responding to color with either the left or right hand, where the location could be compatible or incompatible, EMG revealed muscle activity in the correct hand for button presses. It also showed small activations in the incorrect hand, representing partial errors—intended movements that were inhibited in time [7](#page=7). --- # Animal research methods in neuroscience Animal research is crucial for understanding human neuroscience due to its higher precision in measuring and manipulating neuronal activity, allowing for inferences about human neuroimaging signals [8](#page=8). ### 2.1 Neuronal activity Neuronal activity is based on the resting potential, maintained by the sodium-potassium pump, which results in a negative membrane potential. Signal transmission between neurons occurs via neurotransmitters released at synapses, which open ion channels (Na+ or K+), leading to excitatory or inhibitory stimulation. The summation of these inputs determines whether an action potential, which travels along the axon, is generated in the postsynaptic neuron [8](#page=8). ### 2.2 Measuring and manipulating neuronal activity Techniques in animal neuroscience focus on recording and inducing neuronal and electrophysiological activity very close to cells. This includes using micro-electrodes to isolate single-neuron activity and employing optogenetics, which uses light to manipulate genetically modified neurons. Pharmacological interventions involve using receptor agonists and antagonists, or altering neurotransmitter re-uptake and synthesis. Local field potentials (LFPs) measure the summed dendritic synaptic current in tissues, distinct from action potentials. Intracranial EEG and fMRI are also used in animals, analogous to human neuroimaging techniques [9](#page=9). #### 2.2.1 Recording and inducing neuronal activity via electrodes Micro-electrodes (1-10µm) can isolate the activity of a single neuron by detecting the voltage generated in the extracellular matrix during an action potential, commonly referred to as "spikes". Electrodes are advanced through the brain using a stereotactic reference frame, derived from brain images, to locate target areas. This allows for recordings while animals are freely moving [9](#page=9). * **Example 1:** Neurons in the hippocampus that code for specific head directions have been identified, where certain neurons fire at specific degrees of movement direction, reflecting spatial orientation [9](#page=9). * **Example 2:** Single-cell recordings from dopaminergic neurons in the substantia nigra during reinforcement learning (Schultz et al.) demonstrated changes in firing rates related to reward prediction. An increase occurs with reward delivery, an increase with a conditioned stimulus predicting reward, and a decrease when a predicted reward is omitted. These findings informed human motivation studies using fMRI and PET [10](#page=10) [9](#page=9). The same electrode setup can be used to stimulate neurons, providing insights into regional function and projection pathways [10](#page=10). * **Example:** Electrical stimulation of the septal area in rats (Old & Milder) acted as an operant reinforcer, with rats neglecting basic needs for stimulation, suggesting the existence of "pleasure centers" and linking septal area stimulation to dopamine release in the nucleus accumbens, similar to primary rewards [10](#page=10). #### 2.2.2 Inducing neuronal activity via optogenetic imaging Optogenetics allows for the control and monitoring of individual neuron activities in living, freely moving animals by introducing genes for light-activated ion channels (opsins) via engineered viruses. Blue light activates ON opsins (e.g., channelrhodopsin) to activate cells, while yellow light activates OFF opsins (e.g., halorhodopsin) to deactivate cells. This can be used to induce or inhibit specific behaviors, such as movement or freezing. This method is not applicable to humans due to ethical concerns and infection risks [10](#page=10). #### 2.2.3 Pharmacological manipulations and lesions Pharmacological manipulations and lesions are essential for drawing causal conclusions about the function of specific brain regions or neurotransmitter systems [11](#page=11). ##### 2.2.3.1 Pharmacological manipulations * **Example:** Dopamine depletion using 6-hydroxydopamine injections into the nucleus accumbens (Salamone et al.) revealed dopamine's role in effort-based motivation rather than outcome evaluation. Rats with dopamine depletion avoided effortful choices (crossing a barrier for higher reward) but could still discriminate between reward densities if no barrier was present [11](#page=11). ##### 2.2.3.2 Lesions * **Example:** Lesions of the anterior cingulate cortex (ACC) were studied in relation to effort-based choice (Walton et al.). Rats with ACC lesions, similar to dopamine-depleted rats, ceased climbing a barrier to obtain higher rewards. However, when a barrier was introduced to the low-reward arm, lesioned rats normalized their behavior, indicating that the lesion impaired motivation for effortful tasks when an easier option was available, rather than the general ability to climb [11](#page=11). #### 2.2.4 Local field potentials (LFPs), EEG, and fMRI These techniques offer indirect measures of neuronal activity but are comparable to human data [11](#page=11). * **Local Field Potential (LFP):** Represents a summation of extracellular signals, including synaptic potentials, after-potentials of somatodendritic spikes, and membrane oscillations of nearby cells, but not action potentials of output neurons. LFPs supplement action potential recordings and correlate with signals from non-invasive human neuroimaging methods like EEG and fMRI [11](#page=11). * **Electroencephalography (EEG):** Records activity at a greater distance from neurons and is sometimes performed intracranially in animals [11](#page=11). * **Functional Magnetic Resonance Imaging (fMRI):** Also records activity from a distance [11](#page=11). Combining LFP recordings with EEG and fMRI in animals helps interpret human neuroimaging data by revealing the neuronal basis of these signals [11](#page=11). ##### 2.2.4.1 LFP and EEG Studies comparing EEG and LFP in monkeys during video viewing and a saccade task show similarities between evoked EEG and LFP signals, and between monkey and human EEG signals. This similarity allows for inferences about human EEG reflecting spike rates, similar to monkeys [12](#page=12). ##### 2.2.4.2 LFP and fMRI Recordings of single-unit activity, LFPs, and fMRI in monkeys have demonstrated a correspondence between fMRI signals and LFPs, particularly when considering stimuli of different durations. This provides evidence that fMRI signals reflect hemodynamic adjustments after neuronal activity, related to blood flow and oxygenation. Comparing fMRI data from monkeys and humans reveals similar brain region activation patterns, suggesting that human fMRI signals, like monkey fMRI signals, are related to LFPs [12](#page=12). ### 2.3 General considerations in animal research #### 2.3.1 Rodents versus primates The choice of animal model depends on the research question [13](#page=13). * **Rodents (mice, rats):** Valuable for studying "older" brain structures like the brainstem, basal ganglia, and hippocampus. They are less comparable to humans at the neocortical level and have limitations for complex cognitive tasks. They are cost-effective, easy to breed, handle, and train [13](#page=13). * **Primates (macaques, rhesus monkeys):** More comparable to humans at the neocortical level, making them suitable for investigating higher cognitive functions. However, neuroanatomical differences exist, leading to the use of terms like "monkey homologue". Breeding and training primates are more time-consuming and challenging [13](#page=13). #### 2.3.2 Non-human versus human research Procedures in animal research have fewer restrictions, allowing for a wider range of measures like firing rates, LFPs, receptor binding, and tissue samples, providing closer access to neural substrates and insights into causal relationships through interventions like pharmacological manipulation and lesions. Human research into cognitive functions is more restricted. Techniques available for humans include EEG and fMRI, "virtual lesions" via TMS, studying naturally occurring or therapeutic lesions (e.g., in stroke or epilepsy patients), mild pharmacological manipulations, and neuronal activity recording only as part of therapeutic approaches (e.g., for Parkinson's or epilepsy) [13](#page=13). ### 2.4 Ethical considerations Ethical considerations are crucial in animal research, though less stringent than for human research. Historical unethical practices in human research, such as those under the Nuremberg Code which emphasized informed consent, avoidance of unnecessary harm, scientific foundation, and expert execution, highlight the importance of ethical guidelines. Past research has led to severe harm and loss of life, underscoring the need for strict ethical oversight in all research practices [13](#page=13) . --- # Neuroimaging techniques: EEG, fMRI, and TMS This section provides an overview of key neuroimaging and stimulation techniques, explaining their principles, applications, and limitations. ### 3.1 Electroencephalography (EEG) EEG measures the electrical activity of the brain, offering excellent temporal resolution but limited spatial resolution. It is a non-invasive technique that reflects voltage changes generated by postsynaptic potentials in neocortical pyramidal cells [25](#page=25) [26](#page=26). #### 3.1.1 Principles of EEG * **Neural Basis:** EEG signals originate from postsynaptic potentials (PSPs) in neocortical pyramidal cells, not action potentials (#page=26, 27). Action potentials are too rapid and do not summate effectively for EEG detection [26](#page=26) [27](#page=27). * **Postsynaptic Potentials (PSPs):** These are slower, graded potentials that arise when a neuron is stimulated by another neuron. They affect local ion concentrations and can be excitatory (EPSPs) or inhibitory (IPSPs) [27](#page=27). * **Dipoles:** When a neuron is depolarized by an excitatory signal, there's an influx of ions, creating a separation of charge across a small distance. This charge separation forms a dipole, which is fundamental to measuring neural activity [27](#page=27). * **Summation:** For EEG to detect activity, synchronous dipoles from a large number of aligned neurons (10,000-50,000) must summate. Pyramidal neurons are ideal generators due to their spatial alignment and parallel orientation perpendicular to the cortical surface [28](#page=28). * **Scalp Distribution and Waveforms:** The summed electrical potentials from dipoles spread to the scalp, where electrodes measure changes in voltage over time. The signal strength and polarity at an electrode depend on the dipole's orientation, the electrode's location, and its distance from the dipole [28](#page=28). #### 3.1.2 Data Collection and Analysis * **Electrodes and Reference:** EEG uses electrodes placed on the scalp to measure voltage differences between a reference electrode (in a neurologically inactive area) and the active electrodes [29](#page=29). * **EEG Cap and Systems:** Standardized electrode placement systems, such as the 10-20 system, are used for consistent measurement and cross-study comparability [29](#page=29). * **Signal Acquisition:** The raw EEG signal is a mix of cortical activity and noise (e.g., from muscle movements, heartbeat) [29](#page=29). * **Event-Related Potentials (ERPs):** ERPs are a key analysis method to extract meaningful signals from noise. This involves: * **Segmentation:** Dividing the EEG data into time-locked epochs, usually including a baseline, stimulus, and response period [29](#page=29). * **Averaging:** Averaging across multiple trials. Random noise, uncorrelated with the stimulus, cancels out, while the consistent neural response is amplified. This process can detect signals as small as 1 microvolt (µV) embedded in much larger noise [29](#page=29). * **ERP Waveforms, Peaks, and Components:** * **ERP Waveform:** A plot of scalp-recorded voltage changes over time, reflecting cognitive activity [30](#page=30). * **ERP Peak:** A reliable local maximum (positive or negative) in the waveform, indicating a significant event. Negatives are plotted up, positives down [30](#page=30). * **ERP Component:** A voltage change reflecting a specific neural or psychological process, labeled by polarity (positive/negative) and latency (e.g., P100, N200). For example, the P100 component indicates very fast sensory processing [30](#page=30). * **Visualizing ERPs:** * **Time Domain Plot:** Shows voltage changes over time for individual or averaged electrodes [30](#page=30). * **Topographical Map:** Displays the distribution of electrical potential across the scalp at a specific time point [30](#page=30). * **Mismatch Negativity (MMN):** An example of an ERP component that reliably reflects sensory memory mechanisms and can be modulated by training [30](#page=30). * **(Time-)Frequency Analyses:** Analyzes the oscillatory activity of the brain in different frequency bands (e.g., alpha, beta, theta, delta, gamma). These rhythms emerge from synchronized fluctuations of PSPs in large neuronal groups [31](#page=31). * **Characteristics of Waves:** Frequency (Hz), Power (amplitude/number of neurons), and Phase (timing within the cycle) [31](#page=31). * **Fourier Transform:** A mathematical tool used to represent any time series as a sum of sine waves, enabling the decomposition of brain signals into different frequencies [32](#page=32). * **Clinical Applications:** Used to assess consciousness levels in coma patients and differentiate between states like vegetative and minimally conscious states [30](#page=30). #### 3.1.3 Pros and Cons of EEG * **Pros:** * Cheap and non-invasive [34](#page=34). * High temporal resolution for assessing cognitive process dynamics in real-time (#page=25, 34) [25](#page=25) [34](#page=34). * Direct measure of neural activity [34](#page=34). * Multidimensional (time, space, frequency, power) [34](#page=34). * **Cons:** * Low spatial resolution due to volume conduction and the inverse problem, making precise localization difficult [34](#page=34). * High number of analytical decisions (degrees of freedom) can lead to multiple comparison problems, requiring a priori hypotheses and corrections [34](#page=34). * Unable to measure subcortical activity [29](#page=29). ### 3.2 Functional Magnetic Resonance Imaging (fMRI) fMRI is a popular, non-invasive technique that measures brain activity by detecting changes in blood oxygenation. It offers good spatial resolution and a relatively good temporal resolution, making it valuable for linking brain regions to behavior [36](#page=36). #### 3.2.1 Principles of fMRI * **MRI Basics:** Magnetic Resonance Imaging (MRI) uses magnetic fields and radio waves to create detailed images of organs and tissues. Both structural and functional MRI utilize this technique [36](#page=36). * **Structural vs. Functional Imaging:** * **Structural MRI (e.g., T1-weighted):** Provides clear anatomical detail of the brain [37](#page=37). * **Functional MRI (e.g., T2*-weighted):** Captures changes in brain activity over time during tasks but offers less anatomical clarity [37](#page=37). * **Hydrogen Protons:** MRI relies on the magnetic properties of hydrogen protons in water molecules. These protons align with a strong magnetic field (B0), creating a net magnetization (M0) [38](#page=38). * **Radiofrequency Pulses:** Radiofrequency (RF) pulses are applied to perturb the aligned protons. The subsequent re-emission of energy as the protons realign generates the MR signal (#page=38, 39) [38](#page=38) [39](#page=39). * **Gradient Coils:** These coils introduce magnetic field gradients that allow for spatial encoding, enabling the imaging of specific slices and locations within the brain [39](#page=39). * **T1 and T2 Values:** Different tissues have distinct T1 (longitudinal relaxation) and T2 (transverse relaxation) times, which are manipulated by altering repetition time (TR) and echo time (TE) to create contrast in MRI sequences [39](#page=39). #### 3.2.2 Functional MRI and the BOLD Signal * **Neurovascular Coupling:** The core principle of fMRI is neurovascular coupling: increased neuronal activity leads to increased cerebral blood flow to that region [40](#page=40). * **Blood Oxygenation Level Dependent (BOLD) Contrast:** When a brain region is active, there's an increase in oxygenated hemoglobin supply that exceeds neuronal consumption. This leads to a relative decrease in deoxygenated hemoglobin, altering the magnetic properties of the blood [40](#page=40). * Oxygenated hemoglobin is diamagnetic, causing less magnetic distortion. * Deoxygenated hemoglobin is paramagnetic, causing more magnetic distortion. * This difference affects the T2* decay time of hydrogen atoms near blood vessels, which is measurable by MRI [40](#page=40). * **Hemodynamic Response Function (HRF):** The BOLD signal does not immediately reflect neural activity. It is delayed, typically peaking 4-6 seconds after the onset of neural activity, and involves an initial dip, a peak, and then a return to baseline [41](#page=41). #### 3.2.3 Experimental Design and Data Analysis * **Experimental Design:** Crucial for testing hypotheses. * **Block Design:** Similar events are grouped into blocks. Statistically powerful but can lead to habituation [43](#page=43). * **Event-Related Design:** Events are intermixed, either slowly (long inter-stimulus intervals, ISI) or rapidly (short ISI). Fast event-related designs are more common but require careful randomization of ISIs to disentangle overlapping HRFs (#page=43, 44, 45) [43](#page=43) [44](#page=44) [45](#page=45). * **Data Acquisition:** Involves a localizer scan, a high-resolution anatomical scan, and multiple functional scans (T2*) [46](#page=46). * **Preprocessing:** Essential steps to clean raw fMRI data include slice timing correction, head motion correction, co-registration (aligning functional and structural images), normalization (warping to a standard template like MNI space), and spatial smoothing (#page=46, 47, 48) [46](#page=46) [47](#page=47) [48](#page=48). * **Data Analysis:** * **First-Level Analysis (Subject Level):** Uses the General Linear Model (GLM) to model the BOLD signal in each voxel (a 3D pixel) based on experimental design variables and confounds (#page=48, 49, 50). The output includes beta values representing the contribution of each predictor to the observed signal [48](#page=48) [49](#page=49) [50](#page=50). * **Second-Level Analysis (Group Level):** Tests the hypothesis across a group of subjects using Random Effects (RFX) analysis, often employing t-tests (one-sample or two-sample) [52](#page=52). * **Multiple Comparison Problem:** Performing thousands of statistical tests (one per voxel) increases the chance of false positives. Corrections like False Discovery Rate (FDR) or Family-Wise Error Rate (FWE) are necessary [54](#page=54). * **Region of Interest (ROI) Analysis:** Focusing on pre-selected brain regions to reduce the number of comparisons and test specific hypotheses [54](#page=54). * **Multivariate Pattern Analysis (MVPA):** Analyzes patterns of activity across multiple voxels simultaneously, rather than averaging, to detect subtle differences and potentially "decode" mental states (#page=56, 57) [56](#page=56) [57](#page=57). #### 3.2.4 Pros and Cons of fMRI * **Pros:** * Excellent spatial resolution (millimeters) [55](#page=55). * Harmless and non-invasive [55](#page=55). * Enables testing of precise hypotheses about neuro-cognitive architecture [55](#page=55). * **Cons:** * Low temporal resolution (around 2 seconds) due to the slow nature of the hemodynamic response [55](#page=55). * Measures hemodynamic changes, an indirect proxy for neural activity [55](#page=55). * Expensive (scanner, maintenance, rent) [55](#page=55). * Prone to the multiple comparison problem due to the large number of voxels [55](#page=55). ### 3.3 Transcranial Magnetic Stimulation (TMS) TMS is a non-invasive technique that uses magnetic pulses to temporarily interfere with neural activity in specific cortical regions, allowing for the investigation of causal relationships between brain areas and cognitive functions [64](#page=64). #### 3.3.1 Principles of TMS * **Electromagnetic Induction:** TMS operates on Faraday's principle. A rapidly changing magnetic field generated by a coil induces an electric field in the brain tissue near the coil [64](#page=64). * **Neural Excitation:** This induced electric field can depolarize neurons, leading to action potentials and interfering with ongoing neural activity [64](#page=64). * **Causal Inference:** By stimulating or inhibiting a specific brain region and observing resulting changes in behavior, TMS can establish a causal link between that region and a cognitive function. It is a stimulation technique, not a neuroimaging technique [64](#page=64). * **State-Dependent Effects:** The effect of TMS depends on the state of the neurons at the time of stimulation. Adding "noise" can either enhance weak signals (stochastic resonance) or disrupt processing if the noise level is too high [67](#page=67). #### 3.3.2 Methods and Parameters * **Location of Brain Region:** Stimulation is generally limited to the cortical surface (up to 2 cm depth). Localization methods include [65](#page=65): * **Functional Localization:** Stimulating a known area (e.g., motor cortex) to elicit a specific response (e.g., motor-evoked potential - MEP) [65](#page=65). * **Anatomical Landmarks:** Using anatomical reference points [65](#page=65). * **10-20 EEG System:** Using electrode positions as a guide [65](#page=65). * **Neuronavigation:** Using 3D brain reconstructions to precisely guide coil placement [65](#page=65). * **Coil:** The shape, position, and orientation of the TMS coil significantly impact the focality and depth of stimulation. A figure-8 coil is commonly used for precision [65](#page=65). * **Intensity:** Determined by the maximum stimulator output (MSO%) and often set relative to a subject-specific threshold (motor threshold or phosphene threshold). Stimulating above the threshold generates action potentials, while below it modulates resting potentials [66](#page=66). * **Frequency and Protocols:** * **Single Pulse:** Used for threshold determination [66](#page=66). * **Paired Pulse:** Two pulses with varying inter-stimulus intervals (ISI) to assess intra-cortical inhibition (short ISI) or facilitation (long ISI) [66](#page=66). * **Repetitive TMS (rTMS):** Pulses delivered at a rate of 1-20+ Hz. Low frequencies (e.g., 1 Hz) tend to be inhibitory, while higher frequencies (e.g., 5-20 Hz) are typically excitatory, leading to long-term modulation of cortical excitability [66](#page=66). * **Timing:** * **On-line TMS:** Applied during task performance, with effects lasting only while stimulation occurs [67](#page=67). * **Off-line TMS:** Applied before a task, with effects lasting beyond the stimulation period, often associated with rTMS [67](#page=67). #### 3.3.3 Experimental Designs and Applications * **Motor Evoked Potentials (MEPs):** Measuring MEPs in peripheral muscles after stimulating the motor cortex provides an index of cortico-spinal excitability and can reveal motor monitoring or imitation tendencies [69](#page=69). * **fMRI-Guided TMS:** Combining fMRI to identify peak activation with neuronavigation for precise TMS targeting allows for the study of the causal role of specific brain regions in tasks. This is often referred to as the "virtual lesion" approach [69](#page=69). * **Clinical Applications:** TMS has applications in research and therapy for conditions such as stroke, depression, anxiety disorders, tinnitus, and movement disorders. Clinical effects are thought to involve direct alteration of cortical excitability or indirect effects on connected areas, potentially leading to synaptic plasticity [70](#page=70). #### 3.3.4 Pros and Cons of TMS * **Pros:** * Non-invasive [71](#page=71). * Allows for causal interference with neural activity [71](#page=71). * Good temporal (milliseconds) and spatial resolution (depending on parameters) [71](#page=71). * Generally no long-term side effects [71](#page=71). * Flexible in designing experiments [71](#page=71). * Clinical applications [71](#page=71). * **Cons:** * Shallow stimulation depth (around 2 cm) [71](#page=71). * Requires careful control conditions (sham stimulation) [71](#page=71). * Strict exclusion criteria for safety reasons (#page=70, 71) [70](#page=70) [71](#page=71). * Can be painful or annoying due to muscular twitches [71](#page=71). --- # Neurotransmitter-based methods and clinical applications This section delves into methods for studying neurotransmitter systems, their clinical applications in understanding and treating disorders, and the complexities of combining different neuroimaging techniques. ### 4.1 Neurotransmitter systems The brain utilizes various neurotransmitters to communicate between neurons. Action potentials, rapid electrical signals, trigger the release of neurotransmitters into the synaptic cleft. These neurotransmitters then bind to postsynaptic receptors, either exciting or inhibiting the postsynaptic neuron, thereby influencing the generation of new action potentials [76](#page=76). **Key neurotransmitter categories and examples:** * **Monoamines:** These neurotransmitters have effects that depend on the specific receptor they bind to [76](#page=76). * **Dopamine (DA):** Involved in motivation, learning, cognitive control, memory formation, and motor control. Major pathways include mesolimbic/mesocortical, nigrostriatal, and tuberoinfundibular systems, with additional projections to the hippocampus, amygdala, and cingulate cortex [76](#page=76). * **Noradrenaline (NE):** Associated with arousal, vigilance, attention, and memory formation, with widespread projections throughout the brain [76](#page=76). * **Serotonin (5-HT):** Plays a role in mood, emotion processing, and impulsivity, with widespread projections [76](#page=76). * **Amino acids:** These are consistently either excitatory or inhibitory [76](#page=76). * **Excitatory:** Acetylcholine (ACh), Glutamate, Aspartate [76](#page=76). * **Inhibitory:** Y-aminobutyric acid (GABA), Glycine [76](#page=76). ### 4.2 Methods for studying neurotransmitter systems Neurotransmitter-based methods focus on brain activity at the chemical and synaptic level, offering a contrast to hemodynamic (fMRI) or electrophysiological (EEG) measures [77](#page=77). **Measures used in neurotransmitter-based studies include:** * **Receptor binding:** Assesses the binding of neurotransmitters to postsynaptic receptors (e.g., dopamine D2 receptor PET) [77](#page=77). * **Transporter binding:** Examines the binding to transporter units in the presynaptic membrane (e.g., dopamine transporter PET) [77](#page=77). * **Metabolic spectrum:** Provides a snapshot of molecules within a specific brain region (e.g., GABA MRS) [77](#page=77). While these methods generally have lower temporal and spatial resolution compared to other neuroimaging techniques, they offer crucial insights into chemical and synaptic processes relevant to clinical research [77](#page=77). #### 4.2.1 Positron Emission Tomography (PET) PET is a neuroimaging technique that uses radio-labeled ligands (tracers), commonly containing Carbon (C) or Fluorine (F), to visualize and quantify biological processes [77](#page=77). **Procedure:** 1. A radio-labeled tracer is injected into the participant. 2. The radioisotope decays within the tissue, emitting a positron. 3. The positron collides with an electron, producing two gamma-ray photons. 4. These photons are detected and localized by the PET camera, indicating the site of a receptor binding event. 5. A 3D image is constructed based on the accumulation of these detection events [77](#page=77). Tracer binding potential maps are inversely related to the binding of the endogenous neurotransmitter of interest; higher tracer binding indicates lower actual neurotransmitter binding, as the receptors are occupied by the tracer [77](#page=77). > **Tip:** Transporter-unspecific PET, which assesses cerebral blood flow (CBF) and glucose metabolism (FDG), has largely been superseded by fMRI due to fMRI's superior spatial and temporal resolution [77](#page=77). #### 4.2.2 Magnetic Resonance Spectroscopy (MRS) MRS is an MRI-based method used to assess the regional metabolic spectrum of brain tissue. Unlike standard MRI, which focuses on the spin of hydrogen protons in water molecules, MRS analyzes the resonance of other molecules. The resulting spectrum, measured in parts per million (ppm), reflects the presence of various metabolites associated with neurotransmitters and other brain substances [78](#page=78). **Main MRS metabolites of interest include:** * **N-Acetyl Aspartate (NAA):** An indicator of neuron and axon integrity; a decrease suggests tissue loss or damage [78](#page=78). * **Choline (Cho):** Related to membrane turnover [78](#page=78). * **Creatine (Cre):** Associated with energy metabolism [78](#page=78). * **Glutamate (Glu):** An excitatory neurotransmitter [78](#page=78). * **GABA:** An inhibitory neurotransmitter [78](#page=78). MRS is frequently employed in clinical settings for conditions such as tumors, Alzheimer's, and Parkinson's disease, particularly when studying neurotransmitter metabolites like glutamate and GABA. It can also be valuable in cognitive neuroscience as a covariate for behavioral or neuroimaging data (e.g., fMRI, EEG) [78](#page=78). > **Example:** In a study examining automatic motor control, MRS was used to measure GABA levels in the Supplementary Motor Area (SMA). Higher GABA levels were correlated with smaller behavioral priming effects, suggesting that SMA GABA counteracts automatic responses triggered by subliminal primes [79](#page=79). ### 4.3 Pharmacological manipulations Pharmacological interventions, utilizing agonists (mimicking neurotransmitter effects), antagonists (blocking neurotransmitter effects), and modulators (e.g., reuptake inhibitors), are crucial for developing and validating treatments for neuropsychological disorders. In basic research, mild pharmacological manipulations (e.g., low-dose drugs or dietary changes like tryptophan depletion) are used to explore the relationship between neurotransmission and cognitive functions or personality [79](#page=79). * **Agonists:** Bind to receptors and activate the same intracellular signaling cascades as the natural neurotransmitter, often with greater potency [79](#page=79). * **Antagonists:** Bind to receptors and block them, preventing other molecules from binding and thus inhibiting the natural neurotransmitter's cascade [79](#page=79). * **Modulators:** Influence neurotransmitter systems, for instance, by inhibiting reuptake, thus increasing neurotransmitter availability in the synaptic cleft. > **Example:** Dietary tryptophan depletion, which reduces serotonin synthesis, has been shown to alter motivated behavior. Participants with depleted serotonin levels exhibited slower and more accurate responses in a reward anticipation task, reflecting reduced impulsivity, which has implications for understanding antidepressant drug effects and suicide risk [81](#page=81). > **Example:** PET studies using dopamine antagonist medications in schizophrenic patients have demonstrated varying degrees of striatal dopamine receptor binding. Risperidone showed the strongest effect, indicating significant blockade of dopamine transmission, while clozapine reduced symptoms with less impact on dopamine transmission, correlating with a lower risk of motor side effects [80](#page=80). ### 4.4 Combining methods for enhanced understanding Integrating different neuroimaging techniques provides a more comprehensive understanding of brain function by leveraging their complementary strengths [81](#page=81). #### 4.4.1 fMRI-EEG Combining fMRI (high spatial resolution, low temporal resolution) with EEG (high temporal resolution, low spatial resolution) offers a powerful approach to study brain activity across different timescales and spatial locations (#page=81, 82). Technical challenges include using MR-compatible EEG equipment, synchronizing acquisition, and managing artifacts from the scanner and physiological processes [81](#page=81) [82](#page=82). **Main approaches to combining fMRI and EEG:** 1. **Separate datasets:** Analyze fMRI and EEG data from the same task and participant separately, then compare and correlate findings [82](#page=82). 2. **fMRI as a localizer:** Use fMRI data to guide EEG source reconstruction, improving spatial accuracy [82](#page=82). 3. **Simultaneous fMRI-EEG:** Integrate EEG signals as single-trial parametric modulators within the fMRI General Linear Model (GLM). This approach can provide a "temporal tag" for the fMRI signal, offering better interpretation of the hemodynamic response [82](#page=82). > **Example:** In a Go/NoGo task, including EEG amplitudes (e.g., N2 and P3 components) as single-trial modulators in the fMRI GLM allows for a more precise understanding of the timing and neural underpinnings of inhibitory control [82](#page=82). **Pros of simultaneous fMRI-EEG:** * Complementary spatial and temporal resolution [83](#page=83). * Eliminates between-subject variance and order/practice effects [83](#page=83). * Identical experimental conditions [83](#page=83). * Increased statistical power and ability to covary spatial and temporal brain states on a trial-by-trial basis [83](#page=83). **Cons of simultaneous fMRI-EEG:** * Compromises in study design and technical limitations [83](#page=83). * Increased time for setup and participant discomfort [83](#page=83). * Elaborate artifact correction methods are required [83](#page=83). * Higher statistical and analytical complexity [83](#page=83). #### 4.4.2 fMRI-PET Combining fMRI with PET can link hemodynamic activity to actual neurotransmitter transmission. As PET has very low temporal resolution, studies typically involve separate sessions on different days (#page=83, 84) [83](#page=83) [84](#page=84). > **Example:** A study investigating reward processing found that fMRI activation in dopaminergic regions (basal ganglia) was positively correlated with PET-measured dopamine release during reward conditions. This demonstrated that hemodynamic activity in these areas is linked to actual dopamine transmission [84](#page=84). #### 4.4.3 Transcranial Magnetic Stimulation (TMS) combined with EEG/fMRI/PET TMS, which can create temporary "virtual lesions" or stimulate cortical regions, can be combined with EEG, fMRI, or PET to investigate causal relationships and their impact on neurotransmission (#page=84, 85, 86) [84](#page=84) [85](#page=85) [86](#page=86). * **TMS-EEG:** Reveals causal roles of cortical regions in cognitive processes. For instance, rTMS over the dorsomedial prefrontal cortex (dmPFC) increased errors in a flanker task, suggesting a causal role of dmPFC in conflict resolution and inhibiting wrong response tendencies [85](#page=85). * **TMS-fMRI:** Maps the network effects of stimulating a specific brain region. TMS applied over the parietal cortex enhanced attentional effects in a visual attention task, supporting a causal role for this region in directing attention [86](#page=86). * **TMS-PET:** Investigates the influence of cortical stimulation on neurotransmitter release. Repetitive TMS over motor cortex led to reduced tracer binding in the striatum, indicating increased striatal dopamine release, thus providing evidence for cortical control of dopamine levels [86](#page=86). #### 4.4.4 Pharmacological manipulation combined with other methods Pharmacological interventions can be combined with any neuroimaging technique, though ethical guidelines must be strictly followed. These combinations can reveal how specific neurotransmitter systems influence brain activity and behavior (#page=86, 87) [86](#page=86) [87](#page=87). > **Example:** Pharmaco-fMRI studies have shown that L-DOPA (a dopamine agonist) can reduce performance monitoring activity in the ventral striatum, illustrating an inverted U-shaped relationship between dopamine transmission and cognitive function. Oxytocin was shown to enhance performance monitoring activity in the pregenual anterior cingulate cortex in a social context [87](#page=87). #### 4.4.5 Computational modeling Computational models can be applied to behavioral and neural data to understand cognitive processes like reinforcement learning and response inhibition, often in conjunction with fMRI (model-based fMRI) [87](#page=87). **General Conclusion on Combining Methods:** Combining methods offers a powerful approach to integrate information about space, time, neurotransmission, and causality. However, practical and statistical complexities, including equipment needs, specialized expertise, artifact management, and intricate analysis procedures, must be carefully addressed [87](#page=87). ### 4.5 Clinical applications and research designs Research involving clinical groups is invaluable for understanding neuropsychological disorders, identifying underlying neurotransmitter imbalances, and testing novel treatments (#page=88, 89, 90) [88](#page=88) [89](#page=89) [90](#page=90). #### 4.5.1 Clinical between-group designs These designs compare individuals with a specific disorder or characteristic to a control group, or compare different clinical interventions within patient groups (#page=88, 89) [88](#page=88) [89](#page=89). * **Between-subject design:** Participants are randomly assigned to different groups (e.g., receiving different treatments) (#page=88, 89) [88](#page=88) [89](#page=89). * **Within-subjects design:** The same participants are tested under different conditions (e.g., "on" and "off" medication). This design reduces variance but can be subject to order effects [89](#page=89). These designs provide insights into the development, symptoms, and treatment of disorders, and can reveal neurotransmitter system dysfunctions that inform our understanding of healthy brain function [88](#page=88). > **Example:** Studies on Parkinson's disease patients have shown that L-DOPA, a dopamine agonist, can improve motor control but may impair cognitive functions at higher doses, consistent with an inverted U-shaped dopaminergic medication effect [89](#page=89). > **Example:** Comparing the effects of fluoxetine (serotonin reuptake inhibitor) and desipramine (noradrenaline reuptake inhibitor) in depression revealed that while both are effective for mood, only the serotonin drug had a beneficial effect on episodic memory [90](#page=90). #### 4.5.2 Lesion studies Natural lesions in the brain, occurring due to stroke, injury, or surgery, provide insights into the function of specific brain regions. The principle is that if damage to a region leads to a specific cognitive impairment, that region is likely involved in that function [90](#page=90). **Methodological considerations for lesion studies:** * Ethical neutrality, as damage is natural [90](#page=90). * Homogeneous patient groups and control groups are essential [90](#page=90). * Looking for double dissociations (where damage to region A impairs function X but not Y, and damage to region B impairs Y but not X) strengthens conclusions about independent cognitive processes [90](#page=90). > **Famous Patients:** > * **H.M.:** Resection of his hippocampal cortex led to severe anterograde amnesia (inability to form new long-term memories), providing critical insights into memory systems and the role of the hippocampus [91](#page=91). > * **Phineas Gage:** Damage to his frontal lobe resulted in profound personality changes and social interaction difficulties, highlighting the frontal lobe's role in executive functions and social behavior [91](#page=91). **Limitations of lesion studies:** * Data-driven approach, relying on available patients [90](#page=90). * Lack of precision in lesion extent and location [90](#page=90). * Difficulty in establishing pre-trauma behavior [90](#page=90). * Often involve small sample sizes [90](#page=90). * Interpretation can be complicated by brain plasticity (neural and behavioral adaptation) and the interconnectedness of brain networks [91](#page=91). #### 4.5.3 Intracranial recordings and stimulation In specific medical contexts, such as epilepsy treatment, intracranial electrodes can be implanted, allowing for direct recording (Electrocorticography - ECoG, Stereoelectroencephalography - SEEG) or stimulation of brain tissue (#page=91, 92). These procedures, while primarily therapeutic, can offer unique opportunities for neuroscience research to test hypotheses during or after surgery (#page=91, 92) [91](#page=91) [92](#page=92). * **Deep Brain Stimulation (DBS):** Permanent electrode implantation to deliver electrical impulses to modulate brain activity, used for conditions like Parkinson's disease, OCD, and mood disorders [92](#page=92). * **Vagus Nerve Stimulation (VNS):** Stimulation of the vagus nerve to regulate brain activity, primarily used for epilepsy and thought to modulate noradrenaline transmission [92](#page=92). > **Example:** DBS of the subthalamic nucleus (STN) in Parkinson's disease patients, while improving motor symptoms, has been associated with increased impulsivity, suggesting a role of STN in reward processing and decision-making. VNS has been linked to increased P3 amplitude in EEG, reflecting enhanced noradrenaline transmission in a subset of patients [92](#page=92). ### 4.6 Ethical considerations and combined methodologies When combining methods or using pharmacological interventions, strict ethical guidelines are paramount (#page=86, 92, 93). Research with clinical groups, while providing invaluable insights, can be complex, time-consuming, and often involves smaller sample sizes than typically seen in healthy participant studies. The inherent risks and invasiveness of some procedures, along with limitations on experimental timing, must be carefully considered [86](#page=86) [92](#page=92) [93](#page=93). ### 4.7 Critical views and statistical issues in neuroscience Critical evaluation of neuroscience research is essential to avoid pitfalls such as "neuroenchantment" (overestimating the importance of neuroscience findings), "blobology" (oversimplifying brain function to specific activated regions), and "reverse inference" (deducing psychological states from brain activation) (#page=93, 94) [93](#page=93) [94](#page=94). **Statistical issues that can lead to invalid conclusions include:** * **Multiple comparisons problem:** Performing numerous statistical tests increases the likelihood of false positive findings. Solutions involve adjusting significance thresholds (e.g., FDR, FWE) or defining regions of interest (ROIs) a priori (#page=94, 95) [94](#page=94) [95](#page=95). * **Circular analysis ("double dipping"):** Using the same data to both define an ROI and test a hypothesis within that ROI, leading to biased results and inflated statistical power. Independent ROIs derived from literature, anatomical atlases, or separate data subsets are crucial to avoid this [95](#page=95). * **"Voodoo correlations":** Reporting excessively high correlations (r >.8) between fMRI data and behavioral/personality measures, often due to non-independent analyses. Extracting activity from data-independent ROIs and correlating the mean activity across all voxels with the measure of interest is recommended [96](#page=96). * **p-hacking:** Selectively collecting or analyzing data until statistically significant results are achieved [96](#page=96). * **Excess success:** Reporting findings that appear "too good to be true" based on statistical power estimates [96](#page=96). * **Publication bias:** The tendency for studies with significant results to be published more readily than those with null results, creating a skewed perception of findings [96](#page=96). Increasing transparency through data sharing, preregistration, and publishing null results, alongside critical appraisal of statistical methods, is vital for robust and reliable neuroscience research [96](#page=96). --- ## Common mistakes to avoid - Review all topics thoroughly before exams - Pay attention to formulas and key definitions - Practice with examples provided in each section - Don't memorize without understanding the underlying concepts

| Term | Definition | |---|---| | Skin conductance | A measure of the electrical conductivity of the skin, reflecting sympathetic nervous system activity, often interpreted as an index of arousal intensity. | | Skin Conductance Level (SCL) | A tonic, slow-changing measure of skin conductance during a task, reflecting baseline arousal over time. | | Non-specific Skin Conductance Response (NS-SCR) | Spontaneous, fast changes in electrical conductivity not directly related to a specific stimulus or task, potentially reflecting general arousal. | | Event-Related Skin Conductance Response (ER-SCR) | A phasic change in electrical conductivity that is time-locked to a specific event or stimulus, indicating the body's reaction to particular stimuli. | | Pupillometry | The measurement of pupil size, which can reflect autonomic nervous system activity, arousal, surprise, and mental effort, in addition to reacting to changes in luminance. | | Locus Coeruleus | A region in the brainstem that plays a crucial role in the body's arousal system, with its neuroadrenergic neurons showing a direct link to pupil dilation. | | Electrocardiography (ECG) | A method to record the electrical activity of the heart through surface electrodes, used to measure heart rate (HR) and heart rate variability (HRV). | | Heart Rate (HR) | The number of heartbeats per minute, calculated from the RR interval between consecutive heartbeats, sensitive to emotional processes and physical activity. | | Heart Rate Variability (HRV) | The variation in the time intervals between consecutive heartbeats, reflecting the influence of the parasympathetic nervous system on the heart. | | Impedance Cardiography (ICG) | A method that measures the total electrical conductivity of the thorax and its changes over time, used to derive the pre-injection period (PEP). | | Pre-injection Period (PEP) | The time interval from the electrical stimulation of the ventricles to the opening of the aortic valve, thought to reflect the effect of the sympathetic nervous system on the heart's pumping performance. | | Electromyogram (EMG) | A technique that measures the electrical field changes due to muscle action potentials, allowing for the assessment of muscle activity. | | Blink Reflex | A startle reflex measured by surface electrodes below the eye, induced by external stimulation and integrated by both autonomic and somatic nervous systems. | | Facial EMG | Measurement of electrical activity in facial muscles using surface electrodes above them, used to assess responses to affective stimuli or during cognitive processing. | | Motor EMG | Measurement of electrical activity in peripheral muscles using surface electrodes, often used during cognitive tasks that involve manual responses. | | Neuronal Resting Potential | The electrical potential difference across the membrane of a neuron at rest, maintained by ion pumps like the sodium-potassium pump. | | Action Potential | A rapid, transient electrical signal that travels along a neuron's axon, generated when the sum of synaptic inputs depolarizes the membrane to a threshold. | | Synaptic Transmission | The process by which a neuron communicates with another neuron or target cell across a synapse, involving the release of neurotransmitters. | | Neurotransmitters | Chemical messengers released at synapses that bind to receptors on the postsynaptic neuron, causing excitation or inhibition. | | Local Field Potentials (LFP) | Recordings of the summed synaptic currents within a tissue, representing the collective postsynaptic activity of a neuronal population, not individual action potentials. | | Optogenetic Imaging | A technique that uses light to control and monitor the activity of genetically modified neurons, allowing for precise manipulation of neural circuits. | | Pharmacological Manipulations | The use of drugs or chemicals to alter neurotransmitter systems or neural activity, allowing for causal conclusions about the function of specific brain regions or systems. | | Lesions | Anatomical damage to a specific brain region, whether induced experimentally or occurring naturally, used to infer the function of that region. | | Electroencephalography (EEG) | A non-invasive technique that records electrical activity of the brain from the scalp, offering excellent temporal resolution but poor spatial resolution. | | Event-Related Potentials (ERPs) | Averaged EEG signals that are time-locked to specific events or stimuli, reflecting the brain's response to those events. | | Time-frequency analysis | A method used to analyze EEG data by breaking down the signal into different frequency bands and examining how their power or phase changes over time. | | Fourier Transform | A mathematical technique used to decompose a signal into its constituent sine waves of different frequencies, used in time-frequency analysis. | | Functional Magnetic Resonance Imaging (fMRI) | A non-invasive neuroimaging technique that measures brain activity by detecting changes in blood oxygenation (BOLD signal), offering good spatial but moderate temporal resolution. | | Blood Oxygenation Level Dependent (BOLD) contrast | The signal measured in fMRI that reflects the ratio of oxygenated to deoxygenated hemoglobin in the blood, which changes with neuronal activity. | | Hemodynamic Response Function (HRF) | The characteristic time course of the BOLD signal change following a neural event, typically showing a delayed and sustained increase. | | Block Design | An fMRI experimental design where similar stimuli or tasks are presented in blocks, interspersed with rest periods, maximizing statistical power for detecting sustained activity. | | Event-Related Design | An fMRI experimental design where different stimuli or conditions are presented in a randomized sequence, allowing for the investigation of transient brain responses to individual events. | | Multivoxel Pattern Analysis (MVPA) | An fMRI analysis technique that examines patterns of activity across multiple voxels simultaneously to decode mental states or representations. | | Representational Similarity Analysis (RSA) | An MVPA technique used to measure the similarity between patterns of brain activity evoked by different stimuli or conditions, revealing how information is represented in the brain. | | Decoding MVPA | A type of MVPA where a classifier is trained on brain activity patterns to predict a specific mental state or stimulus. | | Functional Connectivity | The statistical correlation or covariation of neural activity between different brain regions, suggesting that they are functionally linked. | | Resting-state Connectivity | The correlation of spontaneous BOLD signal fluctuations between brain regions when an individual is at rest, reflecting intrinsic functional networks. | | Psycho-Physiological Interaction (PPI) | An fMRI analysis technique used to assess how the connectivity between two brain regions changes depending on a psychological context or task condition. | | Dynamic Causal Modeling (DCM) | A method for inferring the effective connectivity between brain regions, treating the brain as a dynamic system and modeling the causal influences between neural nodes. | | Diffusion Tensor Imaging (DTI) | An MRI technique used to map white matter tracts by measuring the diffusion of water molecules along axons, reflecting structural connectivity. | | Voxel-Based Morphometry (VBM) | An MRI analysis technique used to quantify differences in tissue volume or density between individuals or groups, examining structural differences in the brain. | | Functional Near-Infrared Spectroscopy (fNIRS) | A non-invasive optical technique that measures changes in blood oxygenation and blood flow in the superficial layers of the brain using near-infrared light. | | Functional Transcranial Doppler (fTCD) | A neuroimaging technique that uses ultrasound to measure blood flow velocity in the cerebral arteries, providing an index of brain activity. | | Transcranial Magnetic Stimulation (TMS) | A non-invasive brain stimulation technique that uses magnetic pulses to temporarily interfere with neural activity in specific cortical regions, allowing for causal inferences about brain function. | | Motor Evoked Potential (MEP) | A muscle response recorded via EMG following TMS stimulation of the motor cortex, used to measure corticospinal excitability. | | Virtual Lesion | The temporary disruption of neural activity in a brain region using a technique like TMS, allowing researchers to infer the region's causal role in cognitive tasks. | | Transcranial Electrical Stimulation (TES) | A family of non-invasive brain stimulation techniques that use electrical currents applied to the scalp to modulate neural activity. | | Transcranial Direct Current Stimulation (tDCS) | A form of TES that delivers a weak, constant electrical current between two electrodes (anode and cathode) placed on the scalp to modulate cortical excitability. | | Anodal tDCS | tDCS where the anode electrode is placed over the target brain region, generally increasing cortical excitability. | | Cathodal tDCS | tDCS where the cathode electrode is placed over the target brain region, generally decreasing cortical excitability. | | Transcranial Alternating Current Stimulation (tACS) | A form of TES where an alternating electrical current is applied to the scalp at a specific frequency, aiming to entrain or modulate endogenous brain oscillations. | | Neurotransmitters | Chemical messengers released by neurons to transmit signals across synapses, playing a critical role in brain function and behavior. | | Monoamines | A class of neurotransmitters that includes dopamine, noradrenaline, and serotonin, involved in various cognitive and emotional processes. | | Positron Emission Tomography (PET) | An invasive neuroimaging technique that uses radioactive tracers to measure metabolic activity, neurotransmitter binding, or blood flow in the brain. | | Magnetic Resonance Spectroscopy (MRS) | An MRI-based technique that measures the concentration of specific metabolites in the brain, providing insights into neurochemistry and tissue integrity. | | N-Acetyl Aspartate (NAA) | A metabolite measured by MRS that is considered a marker of neuronal integrity. | | Choline (Cho) | A metabolite measured by MRS related to cell membrane turnover. | | Creatine (Cre) | A metabolite measured by MRS related to energy metabolism. | | Glutamate (Glu) | An excitatory neurotransmitter measured by MRS. | | GABA (Gamma-aminobutyric acid) | An inhibitory neurotransmitter measured by MRS. | | Neuroenhancement | The use of pharmacological or non-pharmacological interventions to improve cognitive functions or mental states. | | Neuroenchantment | The tendency to overemphasize or misinterpret findings from neuroscience, often attributing causal links to brain activity without sufficient evidence. | | Blobology | The practice of interpreting specific fMRI activation "blobs" as directly representing a single cognitive function or psychological construct. | | Reverse Inference | The practice of inferring a cognitive process from the activation of a specific brain region, often based on the assumption that the region is uniquely associated with that process. | | Multiple Comparisons Problem | The statistical issue that arises when performing numerous statistical tests, increasing the probability of obtaining false positive results due to chance. | | Circular Analysis | A type of data analysis where the same data are used to define a region of interest and then to test a hypothesis within that region, leading to biased results. | | Voodoo Correlations | Reported correlations between brain activity (e.g., fMRI data) and psychological measures that are unrealistically high, often due to circular analysis or other methodological flaws. | | p-hacking | The practice of manipulating data analysis or selection criteria to achieve statistically significant results. | | Excess Success | The tendency for reported findings in neuroscience to be "too good to be true," suggesting potential publication bias or analytical issues. | | Publication Bias | The phenomenon where studies with statistically significant or positive results are more likely to be published than those with null or negative findings. | | Default Mode Network (DMN) | A network of brain regions that is typically active during self-referential thought, mind-wandering, and internal cognitive processes, and is less active during externally focused tasks. | | Seed Region | In functional connectivity analysis, a specific brain region whose activity is used as a starting point to investigate its correlations with activity in other brain areas. | | Psycho-Physiological Interaction (PPI) | An fMRI analysis that examines how functional connectivity between regions changes as a function of psychological conditions. | | Dynamic Causal Modeling (DCM) | A Bayesian method for inferring directed causal influences between interacting neural systems, typically using fMRI data. | | Electrocoricography (ECoG) | A neurophysiological monitoring method that involves placing electrodes directly on the surface of the brain to record electrical activity. | | Stereoelectroencephalography (SEEG) | A neurophysiological monitoring method that uses depth electrodes surgically implanted into the brain tissue to record electrical activity. | | Deep Brain Stimulation (DBS) | A neurosurgical procedure involving the implantation of electrodes in specific brain regions to deliver electrical impulses, used to treat various neurological and psychiatric disorders. | | Vagus Nerve Stimulation (VNS) | A therapeutic technique involving electrical stimulation of the vagus nerve, primarily used to treat epilepsy and depression. |