The Brain: Neurons, Impulses, and Neuropsychology PDF

THE BRAIN NEURONS AND GLIA Our entire nervous system is made up of two fundamentally different classes of cell: NEURONS are responsible for conveying tiny electrical impulses around the nervous system and communicating, via synaptic transmission, with other...

THE BRAIN NEURONS AND GLIA Our entire nervous system is made up of two fundamentally different classes of cell: NEURONS are responsible for conveying tiny electrical impulses around the nervous system and communicating, via synaptic transmission, with other neurons or, in the periphery, with muscles. A human brain contains between 100 and 150 billion neurons. GLIA CELLS - Oligodendrocyte -> myelin sheath, it allows faster nerve impulse propagation. - Microglia -> move around the nervous system and remove dead or damaged tissue, and filling what would otherwise be empty space with scar tissue. - Astrocytes -> surround blood vessels in the brain, and are involved in regulating the transfer of substances (glucose, oxygen, hormones, and potentially harmful toxins) between blood and brain. NERVE IMPULSES AND SYNAPTIC TRANSMISSION THE NERVOUS SYSTEMS CNS: Central Nervous System -> brain and spinal cord. PSN: Peripheral Nervous System -> everything else:  Skeletal nervous system: the branch in which neurons carry nerve impulses to voluntary muscles. Autonomic nervous system: the branch carrying nerve impulses to muscles such as the heart, which are not under voluntary control.  Afferent/sensory neurons: carry nerve impulses towards the brain. Efferent neurons: carry impulses away from the brain, towards muscles.  Neurons with myelin sheet: pinky-white appearance -> WHITE MATTER. Neurons without myelin sheet: pinky-grey appearance -> GREY MATTER.  THE CENTRAL NERVOUS SYSTEM The brain coordinates all the body’s functions and consists of 4 regions: the Cerebrum, the Cerebellum, the Brainstem (Hindbrain) and the Diencephalon. ORGANIZATION Somatosensation = Afferent neurons: sensory information from the body (dermatome)→ towards the dorsal regions of the spinal cord → up to the Somatosensory cortex. Motor control = Efferent neurons: motor output from the motor cortex → towards the ventral regions of the spinal cord → down to the innervate muscles. Somatosensory Motor Cortex Cortex Decussation: also called “crossing” descending fibers cross from the left side to the right (and vice versa) at this level in the brainstem to bring about the familiar pattern of contralateral control. CEREBROSPINAL FLUID The Cerebrospinal Fluid (CSF) is a clear, colorless transcellular fluid that circulates around the CNS. It allows the diffusion of nutrients and chemicals from the blood into the space surrounding nerve cells, as well as receiving products secreted by the nerve cells themselves. The CSF protects the brain inside the skull and the spinal cord inside the spinal canal. Functions of CSF = nutrition + cleaning + protection. THE BLOOD SUPPLY Cerebral arteries to supply oxygenated blood. Cerebral veins drain deoxygenated blood from the brain. The blood-brain barrier protects the brain tissue from harmful elements present in the blood, while still allowing the passage of substances necessary for metabolic functions. THE CEREBRUM Organized in two hemispheres (left and right). Delimited by gyrus and sulcus/fissure → the ridges of brain convolutions (parte gonfia) are known as gyri (singular, gyrus), and the valleys between them are called sulci (singular, sulcus) or, if they are especially deep, fissures. Subdivided in 5 lobes → each divided in specialized areas (frontal lobe, parietal lobe, occipital lobe, temporal lobe and insula). Areas are interconnected through the white matter and create functional networks. THE CORTEX It has a bumpy, folded appearance. Its pinky-grey appearance tells us that it is made up primarily of cell bodies, with no myelin sheaths. The cortex is bilaterally symmetrical, which means that the left and right sides are like mirror images of each other. The hemispheres are connected to each other by a number of pathways, of which the largest by far is the corpus callosum. THE LOBES OF THE CORTEX  FRONTAL LOBES: the part of the cortex that is more highly developed in humans. It’s involved in the movement control and in many aspects of behavior, such as planning, generating ideas, problem solving, working memory, and personality.  PARIETAL LOBES: located immediately behind the frontal lobes, and are separated from them by the central sulcus. Somatosensory cortex, which respond to touch sensation from very discrete body regions.  OCCIPITAL LOBES: damage here almost always results in a marked visual impairment, and can lead to cortical blindness.  TEMPORAL LOBES: Three gyri can be identified in the temporal lobe, known as the superior (upper), medial (mid), and inferior (lower) gyri respectively. The superior temporal gyrus is the primary auditory cortex. The right side is involved in interpreting speech sounds, such as tone, rhythm and emotion. The left side in the recognition of language sounds. THE HINDBRAIN MEDULLA The continuation of the spinal cord in the cranium. It contains a series of regions that control basic vegetative processes such as respiration, heart rate, and certain reflexes. Brain death is assessed by the absence of electrical activity in this lowest region of the brain. PONS It’s above the medulla and it’s the main link between the cerebellum and the rest of the brain. It also has a role in certain aspects of both visual and auditory processing and helps to coordinate eye movements in relation to balance. CEREBELLUM It’s in the back part of the brainstem roughly at the level of the ears. It’s concerned with balance, learning and execution of skilled movements, particularly those enacted through time.  THE MIDBRAIN HYPOTHALAMUS It’s involved in controlling behaviors that help the body to maintain an equilibrium or satisfy its needs, such as eating, drinking, temperature regulation, and sex. THALAMUS It’s a relay station for sensory information coming into the brain. The input from a particular modality such as vision enters the thalamus, where it may undergo some preliminary/intermediate processing, before being sent on to the cortex. THE FOREBRAIN BASAL GANGLIA It helps to control movement; it doesn’t directly control it. In combination with the motor cortex, they determine which possible actions actually get put into effect, by permitting some and inhibiting others. LIMBIC SYSTEM It selectively fills behavior with emotional tone, such as fear, anger, pleasure. Damage or abnormal functioning in the limbic system may be associated with both inappropriate emotional responding and impaired detection and/or identification of emotion-laden stimuli, and can also be related to psychiatric disorders including schizophrenia, depression, and anxiety. THE BRAIN DEVELOPMENT 1. Neurogenesis involves generating new neurons from neural stem cells, forming the foundation of cognitive abilities. 2. Cell migration is the movement of cells to their designated locations in the brain, essential for proper brain structure and function. 3. Cell differentiation transforms stem cells into specialized neurons and glial cells, creating a diverse neural network. 4. Cell maturation involves neural progenitor cells developing into neurons and glial cells, forming the brain’s intricate network. 5. Synaptogenesis is the formation of synapses between neurons, driven by experiences and stimuli, crucial for learning and brain function. 6. Cell death and pruning eliminate excess neurons and synapses, refining neural circuits for optimal cognitive function. 7. Myelogenesis forms a myelin, insulating nerve fibers to speed up signal transmission and enhance brain communication. The maximum number of neurons an individual ever has reaches a peak relatively early in life, at 2. The number of neurons appears to remain relatively static throughout childhood and then begins to decline in adolescence, and it has been estimated that by the age of 15 or so, humans are losing thousands of neurons every day. After adolescence there is a progressive reduction of neurons but increase of connections. Brain maturation is related to thinning and pruning.  THE FOUNDATIONS OF NEUROPSYCHOLOGY Neuropsychology is a bridging discipline which principal aim is to try to understand the operation of psychological processes in relation to brain structures and systems. It’s the oldest branch of scientific psychology. Cognitive Neurosciences: investigate the neuro- functional organization of the mind and mental processes (cognitive science) through: - Studies of neuro-cognitive processes in animals (rodents, monkeys…). - Studies of the behavioral and functional correlates of neurologically healthy subjects in developmental, adult and elderly age (Cognitive Psychology). - Studies of the behavioral and functional correlates of brain-damaged patients with neuropsychological deficits in developmental, adult and elderly age (Cognitive Neuropsychology). Neuropsychology: discipline that studies the cognitive, behavioral and emotional-motivational disorders associated with brain lesions or dysfunctions. - Experimental: investigation of the neuro-functional organization of the mind and its neural correlates in relation to a cognitive (dys)function. - Clinical: diagnosis and rehabilitation of these brain disfunctions -> diagnostic and prognostic purposes, patient care and planning, rehabilitation. Neuropsychology is based on the scientific method, fits into the fields of neuroscience and has areas of overlap with psychology, neurology, neuroanatomy, psychiatry, statistics, basic neurosciences… Research methods in neuropsychology: o The study of single cases -> define a model of normal cognitive functioning. o The study of groups -> large case studies, standardized psychometric procedures, analysis of results using statistical methods. A neuropsychologist studies the relationship between the brain and behavior. They focus on understanding how brain and/or cerebral alterations (e.g., injuries, neurological conditions, psychiatric disorders) affect cognitive functions and behavior. The neuropsychologist can be specialized on children and/or adolescents or adults and elderly. - Assessment of cognitive functioning through standardized tests. - Diagnosis in collaboration with other healthcare professionals (traumatic brain injury, dementia, ADHD, learning disorders). - Rehabilitation -> design and implement of treatment plans to help patients regain cognitive functions and improve daily living skills. - Consultation, providing guidance to patients and families, helping them understand the impact of neurological issues and offering strategies for coping and support. - Research, to further understand brain-behavior relationships and to develop new assessment and treatment methods. CAUSES OF NEUROPSYCHOLOGICAL DISORDERS NEUROLOGICAL DISORDERS  HISTORICAL PILLS The importance of the brain as a “behavior control center” was first considered at least 5000 years ago, although the predominant view then, was that the heart was the organ of thinking and other mental processes. The renewed interest in rationalism and science that accompanied the Renaissance in Europe in the 15th and 16th centuries prompted scientists of the day to revisit the brain and to try to establish the functions of particular brain structures. GALL AND THE LOCALIZATION OF FUNCTION Gall was the first one who theorize that different parts of the brain carry out different functions and, conversely, that not all parts of the brain do the same thing -> localization of function. Gall came to the view that each of the two sides of the cerebral cortex consisted of 27 compartments or regional faculties. Accordingly, the more a person used particular faculties, the bigger the brain in that region grew, causing the shape of the skull to be distorted. This is called the science of phrenology: it claimed to be able to describe an individual’s personality and other “faculties” on the basis of the physical size and shape of the skull. Looking at the shape of the skull, if it had a bump somewhere, Gall was supposing that there was a relationship with a specific mental function. Gall was more interested in localization of function within the cerebral cortex (the outer surface of the brain), with its characteristic bumps (gyri) and small and large folds (sulci and fissures), than in the subcortical structures. Gall was the first person to distinguish between grey and white matter in the brain, and also described the first case of aphasia (impaired language production) associated with frontal damage. However, doubts about phrenology first arose when it became apparent that the shape of the skull bore little relationship to the shape of the underlying brain. PATIENT “TAN-TAN” Broca met Monsieur Leborgne, a patient who became known as “Tan” because this was almost the only sound he could utter. The patient was paralyzed on his right side. However, Tan could understand speech well and could, for example, follow quite complicated instructions. When “Tan” died Broca conducted a superficial post-mortem on his brain and confirmed that he had indeed incurred damage to the left frontal cortical region variously attributed to epilepsy, syphilis, or a stroke. This research led him to conclude that language production depended on intact left frontal function, and that the two sides of the brain controlled the opposite sides of the body. Two other examples: - Mister Phineas Gage and personality change. - Being famous without remembering it: the H.M. case. Doctors removed him both of the hippocampus. He was not able to encode and store any new information, but he remembered the past. (Dori) In 1874 Carl Wernicke described two additional forms of aphasia:  Fluent aphasia: the patient could speak at a normal rate but what was said usually made little sense. Caused by damage to the posterior region of the left temporal lobe.  Conduction aphasia: the patient seemed able to understand what was said to them but was unable to repeat it. Caused by a disconnection between the posterior region of the left temporal lobe (Wernicke’s area) and Broca’s area (part of the left frontal cortex). ANATOMO-FUNCTIONAL CORRELATION Traditionally, neuropsychology studies the relationship between cognitive functions and their neurophysiological bases through the investigation of anatomo-clinical correlations. Assumptions: o Different cognitive functions are localized in specific brain regions (localization). o A lesion in a specific cerebral region determines a deficit in a specific cognitive function, and no other functions. We can infer that the specific brain region is the neural substrate of that specific cognitive function. ANATOMO-FUNCTIONAL CORRELATION ANATOMO-FUNCTIONAL DOUBLE DISSOCIATIONS Comparison of two people with brain damage Nowadays, anatomo-clinical correlations are made with more sophisticated techniques (neuroimaging), but the same logical reasoning is applied. Limits: - Different types of lesions can be more/less difficult to be circumscribed, because they have the same symptoms (figure). - Diaschisis effects: damage to one brain area can produce, by loss of excitation, loss of function in brain regions adjacent to or remote from, but connected to, the primary site of damage, inducing a dysfunction in distant nervous system structures. - The effect of brain plasticity -> the brain compensates to regain functions. GESTALT – MASS-ACTION AND EQUIPOTENTIALITY At the beginning of the 20th century European psychology came under the influence of the Gestalt: “the whole as being greater than the sum of its parts”. Theories of:  Mass-action -> the entire cortex is involved in all functions.  Equipotentiality -> each cortical region can assume control for any given behavior. MODULARITY Jerry Fodor argued that it was necessary to distinguish between two classes of cognitive processes:  Central systems -> non-specific in the sense of operating across cognitive domains: attention, thinking, and memory.  Modules -> domain specific in that they only process very particular types of input information, such as color, shape, movement, faces… It presumed that the brain used parallel information processing: the idea that the brain processes two sources of information simultaneously.  METHODS IN NEUROPSYCHOLOGY It is not so straightforward to establish the relationship between the neurophysiological bases of cognitive functions in healthy participants and the symptoms and functions of patients with brain damage. To establish this relationship, we must study on- line the brain at work, both in healthy people and patients. There are different methods which address different questions. Until quite recently, the only options for measurement of brain structure were post-mortem investigation or, very occasionally, biopsy. The latter technique involves the removal and examination of small, but irreplaceable, samples of brain tissue from the brain region in question. It causes inevitable damage to the brain, and therefore it’s hardly ever used in humans. NEUROPSYCHOLOGICAL METHODS ELECTROENCEPHALOGRAPHY (EEG) It records electric activity generated by neurons by using electrodes placed on the scalp. The underlying activity is detected and amplified, and usually displayed on a chart recorder or computer screen. Surface recording is possible because electrical activity in the brain is conducted passively through the meninges (the system of membranes that enclose the central nervous system). The voltages recorded represent the sum of activity from millions of neurons in the area of brain closest to the recording electrode. So, in order to get an idea about the spatial distribution of activity, several separate channels of EEG corresponding to electrodes in different positions on the head can be recorded simultaneously. Meninges For clinical use up to 16 channels are used, while for experimental use 16, 32, 64 or 128 channels. TRACING Amplitude of waves refers to the intensity of the signal, measured in microvolts (µV). Frequency how many waves there are per second, measured in hertz (Hz). Different mental activities correspond to different waves.  Above children. Below adolescent. EVENT-RELATED POTENTIAL (ERP) Event-related potentials (ERPs) are event- related voltage changes in the ongoing EEG activity. A series of stimuli such as tones or light flashes are presented to a participant. The raw EEG for a precise 1-2 second period following each stimulus is recorded and fed into a computer where it is summed and averaged. The ERP describes different stages of processing with extremely high temporal resolution (ms). EXPERIMENT Experimental group: 13 Parkinson Disease (PD) patients “on” and “off” dopaminergic medication. Control group: 13 healthy controls (HC -without dopaminergic medication). ERP task: flanker task. Methods: comparison of performances and ERP amplitudes between the groups and between an “on” or “off” condition in PD patients. Focus on errors, usually followed by frontocentrally distributed negativities (ERPs). Results: PD patients committed more errors than HC, but error rates were not significantly modulated by dopaminergic medication. There were no differences at behavioral level PD patients showed reduced Ne/ERN amplitudes relative to HC. The differences were at the neurophysiological level. Both EEG and ERP have high temporal resolution and low spatial resolution (the of source localization).  MAGNETOENCEPHALOGRAPHY (MEG) MEG has the principles of EEG, but EEG is sensitive to electrical fields generated by extracellular currents (outside the neurons), whereas MEG primarily detects the magnetic fields induced by intracellular electrical activity. MEG involves upwards of 60 electrodes attached to the participant’s scalp, and takes advantage of the fact that when neurons are active, they generate tiny magnetic fields. Event-related fields (ERFs) can be detected by an MEG analyzer accurate means of identifying the origin of particular signals. MEG can therefore locate the source of maximum magnetic field activity in response to stimuli and, map these areas three-dimensionally and in real time. Magnetic fields are analyzed to find the location of the neuronal sources. The MEG, as well as the EEG are suitable for looking at surface structures of the brain. MEG has a very high temporal resolution (msec) and excellent spatial resolution (mm). IN VIVO BRAIN RECORDING In vivo electrophysiology measures very precisely neuronal activity in the brain as either local field potentials or single units. It’s an invasive technique, so it’s often done on animals. NEUROIMAGINING COMPUTERISED TOMOGRAPHY (CT) It provides structural images of the brain. To generate brain scans, low levels of X radiation are passed through an individual’s head at a series of different angles (through 180°). A computer analyses each “image” and generates a compound X-ray. CT scans cannot measure functional activity but they have provided valuable information about structural changes. SINGLE-PHOTON EMISSION COMPUTERIZED TOMOGRAPHY (SPECT) SPECT is a nuclear imaging scan that integrates CT and a radioactive tracer that allows to see how blood flows to tissues and organs. It’s useful for brain injury, for a presurgical evaluation of seizures. The steps are the same as the PET, although the resolution is lower.  MAGNETIC RESONANCE IMAGING (MRI) It depends on the fact that protons in tissue act as little bar magnets that spin. Our body is made up of millions of hydrogen atoms (the human body is 80% water), which are magnetic. When a strong magnetic field is applied externally by the MRI scanner, these spinning protons interact with the external field in a way that produces small but detectable changes in magnetic signal that the scanner can measure. Different types of (brain) tissue have different concentrations of protons and different chemical environments which influence the magnetic properties. Thus, different tissues produce different signals and the scan data can be computer processed to generate images that clearly show, in remarkable detail, the structures of the brain (structural technique). The entire brain can be imaged in successive slices, which can be produced in sagittal (side), coronal (front), or horizontal transverse planes. FUNCTIONAL MAGNETIC RESONANCE IMAGING (fMRI) fMRI is carried out using the same scanner as structural MRI, the magnetic field is perturbed by radiofrequencies. With this method, both structural and functional information can be obtained in a single scanning session. The obtained results are statistical maps. TECHNIQUE Oxygenated and deoxygenated hemoglobin have different magnetic properties. Changes in the relative concentrations of oxygenated and deoxygenated blood therefore produce a detectable magnetic signal:  Deoxygenated hemoglobin is paramagnetic = weakly attracted by externally applied magnetic fields.  Oxygenated hemoglobin is diamagnetic = repelled by externally applied magnetic fields (this is the one that is recorded by the fMRI). The BOLD (blood oxygenation level dependent) provides an indirect measure of neural activity, as neuronal firing has an effect on relative concentrations of oxygenated and deoxygenated blood. Areas of the brain that are more active tend to receive higher levels of oxygenated blood, there is a haemodynamic response: blood releases oxygen to activate neurons at a greater rate (overcompensation). Higher levels of oxygenated blood in a brain area are believed to correspond to a higher neural activity in that cerebral region. LIMITATIONS - The BOLD response occurs over a number of seconds and therefore the millisecond accuracy of EEG or MEG is not possible. There is a low temporal resolution, but a good spatial resolution. - fMRI measures secondary changes in blood activity and metabolism rather than directly measuring neuronal activity. - Using fMRI to make inferences about cognitive processes is only possible if carefully designed, theory-driven experiments are used. Different cognitive/motor task leads to different patterns of brain activation. If a brain region is activated after a task, these two are related. TACTOGRAPHY It’s a structural technique. 3D modeling techniques that image brain pathways using diffusion tensor imaging (DTI) or diffusion spectrum imaging (DSI), two variants of MRI. These techniques map the diffusion of water molecules in the brain. The Tractography (E-F-G-H-I-J) show how the glioblastoma (tumor of the glia cells) changes the structure of the white matter in the brain. POSITRON EMISSION TOMOGRAPHY (PET) PET scanning was the first widely used functional imaging technique and provides images of a person’s brain that show which regions are activated as they undertake different sorts of task, such as reading words, solving mental arithmetic, and listening to music. PET is a nuclear imaging test that integrates computed tomography (CT) and a radioactive tracer that allows to see how body tissues absorb and use different chemicals in real time. TECHNIQUES Injecting subjects with water that has been labelled (it emits gamma rays that are detected by the PET scanner) with the short-lived radio-isotope oxygen 15. When a region of the brain is more active, blood flow to that region increases and therefore more radio-labelled water will be carried to active areas. As the oxygen 15 decays, with a half-life of around 2 minutes, gamma rays are emitted that can be detected by the PET scanner. Another technique is similar to the previous one, but instead of using water, the radio-labelled glucose is used. More active regions of the brain need more glucose, so the radiotracer becomes concentrated in the more active regions. PET is a powerful means of assessing functional brain activity, and it indicates relative levels of, or changes in, activity under different conditions. PET can measure blood flow, blood volume, oxygen usage, tissue pH (acidity), glucose metabolism, and drug activity. It’s useful for:  Detecting the activity of cancer. Because malignant cells grow at a fast rate, they metabolize more sugar than normal cells.  Presurgical evaluation of seizures. LIMITATIONS - PET is a very time-consuming and expensive technique. - It involves exposing subjects to ionizing radiation. - The approach is very limited in terms of temporal resolution: each PET image takes a matter of minutes to generate and represents activity across that period. It is therefore not possible to study activity related to brief or transient stimuli. NON-INVASIVE BRAIN STIMULATION TRANSCRANIAL MAGNETIC SIMULATION (TMS) Transcranial magnetic stimulation (TMS) was originally investigated as a possible treatment in various therapeutic settings; however, it also provides a potential tool for neuropsychologists because it can be used to induce a “virtual lesion”. It’s a method that is able to make both an evaluation and a treatment of cognitive function. TECHNIQUE TMS uses strong pulses of magnetization, by applying a magnetic field on the scalp that can be focally administered via a hand-held coil (stimulator): the tissue underneath the coil is subjected to a current flow that generates activation or inhibition. There is a temporary disruption of the spontaneous neural activity. Thus, different areas of cortex can be stimulated depending on the positioning and the orientation of the coil. DIFFERENT PULSES Single pulses of TMS or brief trains of repetitive TMS at higher frequencies typically increase neuronal excitability. Low frequencies decrease neuronal excitability and are often used to create “virtual lesion”. TMS protocols differ in the number and frequency of pulses delivered. Different protocols are used depending on what has to be analyzed. MOTOR EVOKED POTENTIALS The magnetic pulses induced by TMS over the contralateral primary motor cortex can pass through the scalp and induce a response known as “motor evoked potential” (MEP) in the target muscle. This response can be recorded using surface electromyography (EMG) electrodes placed over the muscle of interest. TMS is better suited for the investigation of superficial brain regions (the cortex for example) than for probing less accessible regions and deeper structures.  TRANSCRANIAL ELECTRICAL STIMULATION (tES) These techniques aim at modifying the excitability of a target area generating a current flow through the cortex: neuromodulation. No action potential is generated; the excitability of the cortex is modulated. TRANSCRANIAL DIRECT CURRENT STIMULATION (tDCS) EXPERIMENTAL PROTOCOLS Offline stimulation involves a period of pre-stimulation in which a task may be completed, followed by a period of stimulation and then a post-stimulation task (A), or a period of stimulation followed by a post-stimulation task only (AB). Online stimulation involves participants receiving stimulation during a cognitive task (C). Sham stimulation, the task can be applied at any point during the session (D), without saying this to the participants, depending on whether an online or offline protocol is undertaken. This is usually used for the control group. INVASIVE BRAIN STIMULATION DIRECT ELECTRICAL STIMULATION (DES) It is an invasive tool used for example for mapping cognitive functions while patients are undergoing awake neurosurgery or invasive long-term monitoring to identify epileptogenic tissue.  COGNITIVE NEUROSCIENTIFIC TECHNIQUES All the previous techniques can be subdivided in:  Correlational methods – Assessment: there is a correlation between activities and activation in the brain. (EEG, MEG, MRI, fMRI, PET).  Causal inference – Assessment and treatment: if you modify the excitability of a target area, and this stimulation or modulation influences the behavioral performance, then that specific area is crucial for that cognitive function (TMS, tES). Each cognitive neuroscience technique has its limits and potentials. It is crucial to integrate them when addressing research questions. Ex. combination of fMRI + EEG to get both high temporal and spatial resolution. Ex. combination of fMRI + TMS to obtain good localization and causal inferences. GENERAL PRINCIPLES FOR NEUROCOGNITIVE STUDIES They’re similar to those applied in all fields of experimental psychology.  The more the better, group studies are preferred: many participants and many trials per participants (at least in studies with healthy participants/control groups).  Comparisons between at least an experimental and at least a control condition are needed.  Construct validity: Is my behavioral measure the correct operationalization of the cognitive process that I aim to study? Has my technique the correct spatial resolution to target the specific brain area of interest? Has my technique the correct temporal resolution to capture the process I am interested in? What are the intrinsic limits of my techniques (contraindications, movement constraints, costs…)? NEUROPSYCHOLOGICAL ASSESSMENT The neuropsychological approach relies on using tests designed to reflect, usually in a relatively specific way, different aspects of cognitive function. Poor performance on a test may indicate localized brain damage. Poor performance on a series of tests may reflect a widespread damage. Neuropsychological assessment serves several purposes:  It can give a “neurocognitive” profile of an individual, identifying both strengths and weaknesses in cognitive performance.  Repeated testing over time can give an insight into changes in cognitive functioning that may relate either to recovery after accident/injury or to the progression of a neurological illness. AIM Diagnostic: - discriminate between different conditions. - provide diagnostic information in cases of negative neuroradiological data. Prognostic: provide information on the outcomes of certain pathologies. Patient care and planning: - inform the patient of his cognitive state to understand the alterations resulting from the disease. - inform family members so they can understand and adapt to the condition. - evaluate the effects of medical therapies on the patient's cognitive efficiency. - evaluate their degree of daily autonomy and the opportunity of a rehabilitation intervention. Rehabilitation: provide the starting point for a therapy, planning and managing a therapeutic program and evaluate its short and long-term effectiveness. Medical legal: - diagnostic: (is it a consequence of…? Is there reason to suspect that brain damage…?) - description of the patient condition: (will it prevent him from working?) For research: single evaluation during a protocol or pre- and post-treatment. 1. Demographic data and cognitive-behavioral history: o Obtain information on why and to whom the patient was sent (general practitioner, hospital, assistance center operators, clinical psychologist). o Know the disease onset and its evolution. o Know the type of life the patient leads or led before the pathology. o Understanding the premorbid personality. o Know the health of close family members. o Know the outcome of the examination of elementary neurological functions performed by the neurologist (know of peripheral hearing or vision deficits). o Know the outcome of the main instrumental investigations (ex. MRI, PET) and other medical tests. o Know any premorbid cognitive difficulties (even developmental) 2. Patient interview, in order to clinically evaluate: - Speech and comprehension skills. - Mood tone. - Attentional skills. - Awareness of deficits or illness. - Explain the purpose of the exam and what it consists of. 3. Administration of standardized tests/test batteries. In a typical neuropsychological assessment, a series of tests (called a test battery) will be given. These measure verbal and non-verbal intelligence, language, tactile and manipulative skills, auditory sensitivity. In addition, specific measures may be adopted to test particular hypotheses about an individual. For example, if the person has received brain damage to his/her frontal lobes, tests might be selected that are known to be especially sensitive to frontal damage.  Wechsler Adult Intelligence Scale (WAIS-R) -> particularly useful for studying selective deficits because the 14 component subtests address a wide range of psychological functions.  Wisconsin card sort test -> assesses spatial memory.  Cambridge Automated Neuropsychological Assessment battery (CANTAB) -> non-verbal test aimed at assessing executive and memory functions. 4. Interview with caregivers/families:  Know the patient's family environment.  Know how the patient behaves when he/she is at home.  Make family members aware of the situation and its evolution.  Provide them with the correct interpretation of the patient’s test and behavior. Possible second visit with more ad hoc and ecological tests, to better define the diagnosis. The use of neuropsychological tests in combination with in-vivo techniques promises to be one of the most informative research approaches. Converging operations: the use of several research methods to solve a single problem so that the strengths of one method balance out the weaknesses of the others. Neuropsychological testing has gained considerable respect in recent years. However, it would be wrong to think that a battery of neuropsychological tests alone could somehow provide the researcher or clinician with a complete map of brain functioning. A few concerns raised about the neuropsychological testing:  As individuals recover from brain damage, they often develop alternative strategies or techniques to overcome remaining deficits.  Ecological validity of the tests, because patients’ performance on neuropsychological tests can, in fact, be inconsistent with their performance in everyday life. CLINICAL NEUROPSYCHOLOGY TREATMENT Cognitive rehabilitation is based on the assumption of the plastic nature of our brain: functional reorganization and (re)learning after a cerebral lesion. The term brain plasticity refers to the property of the brain to vary structure and function along development and during adult life, in constant interaction with the outside world (environment). Plasticity concerns the changes in the nervous system organization that underlie various forms of short- and long-term behavioral modification; they include the processes of maturation, adaptation to changes in the environment, specific and unspecific learning, and the compensation mechanisms. - Positive plasticity -> resource. - Negative plasticity -> maladaptive. STRUCTURAL NEUROPLASTICITY  Neurogenesis: the process by which neurons are generates. Sprouting, when new axon and dendrite extensions Rerouting, when new connections are made allow existing neurons to form new connections. between active neurons to create alternate neural pathways. FUNCTIONAL NEUROPLASTICITY  Long-term potentiation (LTP) is defined as a persistent strengthening of synapses based on recent patterns of activity.  Long-term depression (LTD) is defined as a persistent decrease in synaptic strength depending on specific stimulation. Rehabilitation capitalizes on brain positive plasticity (resource) to reduce the negative effects of a brain damage. o Cognitive remediation: it’s based on a restorative model that attempts to reduce or eliminate impaired cognition by re-gaining the cognitive function. Ex. if I have a stroke, I can remediate. o Compensatory techniques: compensate for, or circumvent cognitive deficit, with reliance on intact cognitive skills and strategies and supports for working around cognitive deficits. A reduction of the disability is gained through: - Internal self-management strategies. - External strategies/environmental modification. - Errorless learning. PHYSIOTHERAPHY Physiotherapy aims to restore body function that has been lost through disease, injury, disability, or ageing. The therapist will probably employ a raft of techniques to achieve this: exercise, massage, manipulation, and increasingly, technological procedures such as ultrasound. Randolph Nudo conducted research on animals regarding the recovery of function following circumscribed strokes, which typically lead to a permanent loss of tissue in the vicinity of the stroke itself, and a ring of adjacent tissue whose functioning, while initially compromised, may recover over time. Localized strokes were deliberately induced by manipulating blood supply to the “hand” area of the motor cortex. Five days later the researchers initiated a regime of “physiotherapy” in which the stroke-induced monkeys had to pluck hundreds of tiny food pellets from different-sized containers for several hours each day. Exercise was associated with both a greater recovery of function in the affected hand and with a reduction in the amount of long-term damage (tissue loss) in the penumbra region adjacent to the stroke site.  BRAIN DIFFERENCES AND LATERALISATION Despite their superficial similarity, the two hemispheres of the human brain consistently differ in a number of characteristic ways. PHYSIOLOGICAL DIFFERENCES - The right frontal region typically projects further forward and is wider than the left frontal region. The reverse pattern is seen in the occipital lobes. - The Sylvian fissure extends further back horizontally on the left side than the right. - The planum temporale is larger on the left side than on the right. - Cells in the Broca’s area have many more synapses than the equivalent region on the right side. - The angular gyrus, which may be important in reading and semantic aspects of language, is larger on the left than on the right side. UNILATERAL NEUROLOGICAL DAMAGE Damage to the left hemisphere seems to result in a greater impairment to language-related skills. A stroke affecting the left hemisphere frequently leads to aphasia. The right hemisphere damage can lead to deficits in spatial skills such as mental rotation, map reading, orientation.  SPLIT-BRAIN SYNDROME Over a period of several years about 100 people underwent “sectioning” of the corpus callosum. In some cases, the lesion was partial; just the anterior or posterior region would be cut. For some patients, however, complete sectioning was performed, rendering the two hemispheres anatomically almost completely isolated from one another. Many individuals were assessed on batteries of psychological tests both before and after their operations. Post-surgery, some patients were initially hemiplegic, mute, and confused, but after a period of recovery these features abated, and both the intensity and frequency of epileptic activity were almost always reduced, with some patients no longer experiencing major seizures at all. Moreover, patients’ IQ scores and scores on many other tests often improved and most people claimed to feel better too. EXPERIMENTAL STUDIES In higher mammals, including humans, most visual information from the right visual field (that is, everything to your right if you look straight ahead) travels from both eyes, via the visual pathways, to the left occipital lobe. Auditory and somatosensory input is also predominantly “crossed”. Sperry and colleagues were interested to know what would happen if information was presented to the split-brain patient one hemisphere at a time. They presented visual stimuli very briefly to either the left or right. After each presentation the participant had to say what (if anything) they had seen. Sometimes, they were also given the opportunity to reach behind a screen to feel items (with either their left or right hand). If a picture of a car was flashed to the right of the fixation point, the patient reported seeing a car. The image travelled to the left (talking) hemisphere. If the same picture was flashed to the left of the fixation point, the patient usually reported seeing nothing: now the image went to the “non-speaking” right hemisphere. However, if the patient was allowed to reach behind a screen with their left hand, they could usually select a model car from among other out-of-sight objects. The split-brain studies support the idea of a key role for the left hemisphere in linguistic skills. The left hemisphere may be better than the right at processing familiar faces, whereas the right hemisphere seems specialized for dealing with unfamiliar or novel faces. CALLOSAL AGNESIS A small number of people are born with a grossly malformed or entirely missing corpus callosum; this disease is called callosal agenesis. Research on a-callosal children has indicated that they too have language skills lateralized to the left hemisphere, and spatial skills lateralized to the right. However, people with callosal agenesis do have certain difficulties with aspects of both language and spatial processing. They’re very clumsy in tasks that require bimanual cooperation, such as playing a musical instrument, doing certain sports…  PROCESSING STYLES APPROACH The “processing styles” approach affirms that the main functional difference between the hemispheres is not so much “what” they process, but “how” they process it. The left hemisphere is specialized to process information in an “analytical-sequential” way, whereas the right hemisphere adopts a more “holistic-parallel” mode of processing. Both hemispheres will be involved in linguistic and spatial tasks but that they will differ in the type of processing that is undertaken. Language is both:  Sequential because word order is critical for meaning.  Analytical because the meaning of spoken language depends on breaking up what is, in effect, a continuous stream of verbal sounds in order to identify words and understand the message. HANDEDNESS AND LATERALIZATION The hand we use to write is usually indicative of our hemispheric dominance: who’s right-handed usually has a left-hemispheric dominance for language. Left-handers with damage to the right hemisphere are more likely to experience language problems than righthanders with similar damage. Spatial skills are more likely to be affected after right hemisphere damage in right-handers than in left-handers. GENDER DIFFERENCES Structurally, female brains are slightly lighter, but contain proportionately more grey matter (cell bodies and dendrites). Male brains have more white matter and larger ventricles. There are also particular local differences in the structure of the hypothalamus, some of which are linked to hormonal differences between the sexes. At birth the general level of tissue development in boys is between 4 and 6 weeks behind that of girls, and they are known to be about twice as likely to be born with a range of neurodevelopmental disorders as girls. Cognitive developmental disorders including autism, hyperactivity, stutter, aphasia, and dyslexia are all four to six times more common in boys. Girls tend to do better than boys at language-related tasks, such as comprehension, fluency, and translation; and that boys at visuospatial tasks, such as visual tracking, maze learning, mental rotation. The appearance of some differences so early in development suggests that they are, in part, a consequence of differential brain organization. Left-sided damage was more likely to result in impaired language function in men than women. Right-sided damage was more likely to impair visuospatial function in men than women. Although the brain’s overall structure is highly individualized, and these findings reflect general trends rather than strict rules.  VISUAL OBJECT RECOGNITION AND SPATIAL PROCESSING Sensation (V1): when sensory receptors detect sensory stimuli. Sensory receptors are specialized neurons that respond to specific types of stimuli. When sensory information is detected by a sensory receptor, sensation has occurred. Visual sensation is about input “getting registered” in the brain. Transduction: the conversion from sensory stimuli to action potentials; it represents the first step toward perception. Perception (V4): the organization, interpretation, and conscious experience of those neural pieces of information. It organizes sensations into complex representations. Not all sensory stimuli are perceived, and then become conscious; our perceptions are affected by various factors, including beliefs, values, prejudices, and previous experiences. VISUAL PATHWAYS Up to half of the cerebral cortex is directly or indirectly involved in visual processing. Visual pathways: ganglion cells of the retina -> optic nerves - > optic chiasm -> lateral geniculate nucleus (LGN) of the thalamus -> V1 -> associative visual cortices (V2-V5). Visual pathways carry the information segregated:  Spatially (retinotopic organization).  Qualitatively (color, shape, movement). V4: color processing. Lesion -> achromatopsia. V5: movement processing. Lesion -> akinetopsia. ACHROMATOPSIA Cerebral achromatopsia = acquired color blindness (you’re not born with it) due to a bilateral lesion of V4 (physical trauma, hemorrhage or tumor). Stimuli discrimination based on their luminosity is preserved. So, patients are not able to see the color, but are still able to see the luminosity (you see the different shades of gray). Peripheral achromatopsia = cone photoreceptors dystrophy (inherited, present from birth) generates markedly reduced visual acuity, extreme light sensitivity, and the absence of color discrimination. It’s related to sensory. AKINETOPSIA Cerebral akinetopsia = acquired motion blindness due to a bilateral lesion of V5. It’s like perceiving the world in frames, similar to a strobe lights situation.  WHAT AND WHERE – VENTRAL AND DORSAL PATHWAYS In the mammalian brain there is extensive output from the occipital lobes to other cortical regions that is carried primarily by two major pathways. The inferior route follows a ventral course (round the side and particularly underneath) into the temporal lobes, whereas the superior route takes a dorsal course (over the top) into posterior regions of the parietal lobes. VENTRAL STREM – WHAT Specialized for object recognition; it’s the vision for perception. Neurons in posterior regions (at the beginning of the stream) fire in response to relatively simple stimulus characteristics such as width, shading, and texture, whereas neurons later on in the stream only respond to much more complex visual stimuli. Neurons further forward along the stream are less concerned with the physical position of objects in the visual field. Cells in this stream make considerable use of color. This is important for object recognition also because it often allows us to distinguish figure from ground. Pargo cells: small cells, gives information about details (shape, color…) DORSAL STREM – WHERE Specialized for spatial perception. Localization in space and guide for movement, it’s the vision for action. Magno cells: big cells, give information related to movement, localization, speed... The two streams operate in parallel to allow us to address the fundamental questions of “what” we are looking at, and “where” it is located in our field of vision. Double dissociation: these pathways work together, so if one is damage, the other works fine, but there is a dissociation of the two. Limits of double dissociation - Cerebral lesions are not linear. Damage in one area might also disrupt functions in other areas. - Third way for biological movement and social perception. This pathway complicates the double dissociation model, as it suggests that perception of objects and spatial relations isn’t confined to just two distinct pathways. Instead, brain functions may be distributed across multiple routes, integrating different types of sensory and contextual information. - Intra- and inter-talk between the systems. Pathways are communication within and between them and double dissociation tend to focus on isolated functions. Because these two pathways are specialized for processing different types of visual information, damage to each pathway leads to distinct impairments without affecting the other.  VISUAL AGNOSIA Deficit in the Ventral system The deficit is independent of sensory impairment (spared sensation and processing in primary cortices), mental deterioration, deficit in attention, memory, or aphasic syndromes. Thus, it is a disorder of the cognitive processing of stimuli that generates an impaired recognition. The subject is not able to recognize and identify a given object, scent, shape, person or entity, despite maintaining his/her sensory abilities. Recognition is spared in other sensory modalities. In the 1890s, Lissauer described two forms of object recognition failure which he called apperceptive and associative agnosia. Today, we think that the two disorders are linked to damage at different stages in the ventral stream. APPERCEPTIVE AGNOSIA Usually associated with right occipito-parietal damage. The elementary sensory functions (such as the recognition of color and size) are preserved, although there is the inability to integrate elementary sensory data in complex and structured visual perceptions, distinct from the background. There is the inability to identify an object, copy an image, to describe the details or singular elements of a stimulus, or to distinguish an object from others. It’s a perceptual disorder. Patients may be presenting a linear drawing instead of the real object, overlapping multiple figures of objects in space, or presenting the patient with incomplete, masked or degraded images, unusual perspectives, or silhouettes. Patients are unable to follow the contours of objects with fingers, to make a copy of a drawing, since they cannot form a well-structured percept. Although, drawing from memory is generally possible, because there is an integrity of the knowledge relating to the visual aspects of the object. ASSOCIATIVE AGNOSIA Usually associated with occipito-temporal lesion in the left hemisphere or bilaterally. The patient is not able to identify a given object. Normally, at a cognitive level, the perceived object is compared to the knowledge accumulated by the subject in the semantic memory, but the patient is not able to recognize the object, to remember its name, nor its correct use. Example: the examiner shows a glass. The patient perceives the glass, but is not able to recognizes it, remember its name and its use. However, when the examiner asks to the patient to verbally describe what a glass is, the patient answers correctly. The perceptual visual analysis is preserved, but there is a disconnection between the perceptual analysis and the semantic store. The patient can discriminate objects but not identify them, copy drawings, sort object by category. They cannot name objects (language is spared), retrieve the use of an object and all its related functional features, and may not be able to drawn objects from memory. ASSESSMENT AND TREATMENT OF VISUAL AGNOSTIC PATIENTS Assessment steps: o Demographic data and cognitive-behavioral history. o Interview with the patient and caregiver(s)/relative(s). o Administration of standardized tests/test batteries. Copy test: o Size judgment of geometric figures (early visual processing). o Poppelreuter's Superimposed Figures Test (early visual processing). o Coupling of objects in different perspectives (switching from an observer-based representation to an object-based one). o Reality decision task (structural description stored in memory). o Figure-figure association (conceptual knowledge). o VOSP (Visual object and space perception battery; Warrington and James, 1991). o BORB (Birmingham object recognition battery; Riddoch and Humphreys, 1983). RIDDOCH AND HIMPHREYS’ COGNITIVE NEUROPSYCHOLOGICAL MODEL OF OBJCET RECOGNITION 1. The generation of a unified “primal sketch” from the two 2D retinal images. It includes information about boundaries, contours, and brightness fluctuations, color, depth but not overall form. 2. The generation of a 2.5D image. It contains information about form and contour, but neither object constancy (recognizing an object as such whether it is near or far away, or even upside- down) nor perceptual classification. 3. The 3D representation, a true object-centered mental representation. 1. 2. Incomplete, overlapped, embedded figure/letters. Unusual perspective. 3. Chimeric figures, object decision task (real/unreal).  PLACE AGNOSIA A special case of visual agnosia, the inability to recognize places, which yet can be retrieved, for example after verbal description. There is no memory deficit. Often associated to prosopagnosia and achromatopsia. COLOR AGNOSIA A special case of visual agnosia, the deficit in color naming and/or color-object association. Patients can see colors, they’re just unable to name them. In the absence of achromatopsia, there is the amnesia for colors or aphasia for colors. PROSOAGNOSIA Right or bilateral lesion in occipito-temporal inferior cortices Prosopagnosia, or face blindness, is a cognitive disorder of face perception in which it is impaired the ability to recognize visually-presented faces of known/famous people, including one's own face (self- recognition). In some cases, people may be unable to match pairs of faces, or say whether two photographs are of the same individual. In other cases, recognition of particular individuals such as film stars or members of the person’s own family may be affected. In the most extreme and perplexing form of the disorder, the person may even lose the ability to recognize themselves from photographs or in the mirror. Faces are recognizable in other modalities or by "feature-by-feature" recognition strategies involving secondary clues (glasses, hat, clothing, walking pattern, hair color, mustache, skin color, body shape, voice). Facial parts, other aspects of visual processing (such as object discrimination), intellectual functioning (such as decision-making), or memory abilities are intact. Studies have shown that 1 in 50 people have some form of prosopagnosia, with developmental being the most common. Many people with prosopagnosia also show other abnormalities of object recognition, and when these conditions coincide the prosopagnosia is, typically, more severe. NEURAL CORRELATION Structural and functional components of the face-processing system. There is an involvement of both gray matter and white matter (connections). APPERCEPTIVE PROAGNOSIA Related to earliest processes in the face perception system; and it’s due to a damage in right occipital temporal regions, especially in the fusiform gyrus (Occipital Face Area). People with this disorder cannot make any sense of faces and are unable to make same–different judgments when they are presented with pictures of different faces. Patients are unable to recognize both familiar and unfamiliar faces; have difficulty in recognizing facial emotion. Possibility of facial recognition based on non-face clues, such as clothing, hairstyle, skin color, or voice. ASSOCIATIVE PROAGNOSIA Spared perceptual processes but impaired links between early face perception processes and the semantic information humans hold about people in their memories. Damage in right anterior temporal regions (Fusiform Face Area) may play a critical role in associative prosopagnosia. Patients are able to tell whether photos of people's faces are the same or different and derive the age and sex from a face (suggesting they can make sense of some face information). They have difficulty in identifying the person or provide any information about them such as their name, occupation, or when they were last encountered. Behavioral (eye movements) and electrophysiological (ERP) studies have shown that the absence of conscious recognition of faces can be accompanied by an unconscious recognition of them. o Overt recognition -> conscious. o Covert recognition -> unconscious. Two-route model of face recognition:  The ventral route (identification detector) is responsible for overt recognition.  The dorsal route (significance detector) is responsible for covert recognition. Prosopagnosia would consist in a deficit of the ventral pathway. ASSESSMENT Matching Faces Task (Benton Facial Recognition Test). Faces are presented from different perspectives. It consists in an evaluation of perceptual processing. “Please order the picture according to age” -> apperceptive agnosia. “Please tell me which picture is familiar with you (VIPs or relatives)” -> associative agnosia. Association between face and stored knowledge. Naming “who is him?” -> associative agnosia. Language. Judgment of facial expression -> associative agnosia. TREATMENT - Analysis of visual features. - Face matching. - Face discrimination. - Photo-name association. - Categorization of faces (presentation of faces belonging to the same occupational category, recognition of the category they belong to and therefore recognition). - Memorization techniques (association of salient feature, name occupation for learning of unfamiliar faces; verbalization of relevant aspects of the person during the presentation of the familiar face). - Caricature presentations. - Semantic associations. CAPGRAS DELUSION In 1923 Capgras and collaborators described a psychiatric symptom in which the patient believes that the most significant (friend, spouse, parent, another close family member, or pet) people have been replaced by lookalikes (impostors, robots or aliens), despite recognition of familiarity of their behavior and appearance. Since the 1980s, the Capgras delusion has been reported in neurological patients. It’s not a deficit in perception or recognition of faces, but disconnection with the emotional recognition. It is resistant to logical-rational explanations. The delusion most commonly occurs in individuals with schizophrenia or neurological patients after brain injury or neurodegenerative diseases, as dementia with Lewy bodies and other forms of dementia.  AUDITORY AGNOSIA The inability to recognize sounds, typically nonverbal sounds, even if patients have an adequate hearing, there are no problems on the sensory level. Patients have to associate a sound to the object/event that usually produces it. There is a distinction between apperceptive and associative agnosia, but very few cases described in scientific literature. TACTILE (SOMATOSENSORY) AGNOSIA The inability to recognize objects from touch, that is integrate/identify tactile representations of items. It takes place in patients with adequate somatosensorial sensations indicating no elementary somatosensory loss, and no damage to the afferent pathways. There is a distinction between apperceptive and associative agnosia, but very few cases described in scientific literature.  Dorsal Pathway BASIC SPATIAL PROCESSES Spatial perception leads to the ability to form and manipulate an internal representation of the outside world, and in some cases, to locate oneself in it. This consists in different abilities: o Localizing points in space: difficulty in reaching toward a visual stimulus. o Depth perception. o Line orientation and geometric relations. o Motion. o Mental orientation: spatial perception and the production or generation of some tangible outputs. o Constructional skills. o Route finding. o Spatial memory: higher-level processing, critically dependent on visual perception and visual experience. Spatial processing is subserved by the dorsal or Where stream, that terminates in the parietal lobes. Damage to this stream affects the perception of objects in space, detection of motion, and mental rotation (lower level of cognitive functions). This stream interacts with other cortical regions to mediate spatial constructional skills, route finding, and spatial memory (higher level of cognitive functions). The hippocampus is also a crucial structure in route finding. Most of spatial processes are related to the right hemisphere, except for Motion (bilateral V5 and surrounding areas). Nevertheless, the left hemisphere can make important contributions to the overall processing through the employment of complementary processing styles, detectable especially after brain injury. Distinct movement-processing can be affected → possible presence of double dissociation. There is a strict relationship with other cognitive functions, especially memory, attention and working memory, because the dorsal pathway has many connections with the frontal lobe. Affordances: indicate the action possibilities offered by objects, independent of the visual features that allow their recognition (color, texture…).  OPTIC ATAXIA Disorder of coordination and accuracy of visually- guided movements (command or copy). Patients can execute body-oriented movements normally, compensating for defective visual control by using somatosensory cues. It’s not related to motor, sensory, visual acuity, or visual field deficits. Object recognition is usually out of danger. The difficulty is in reaching for objects or imitating movements. BALINT-HOLMES SYNDROME Following a bilateral occipito-parietal lesion, this syndrome includes:  Optic ataxia.  Simultanagnosia.  Oculomotor apraxia: paralysis of the eye fixation with inability to look voluntary into the peripheral visual field. Difficulty in visual scanning and maintain fixation on an object.  Anosognosia -> usually patients are not aware of having this deficit. Patients are not blind and can actually “see” objects anywhere in the visual field if they can direct attention to that location. When shown a complex meaningful picture patient could identify different elements of the picture as his attention switched involuntarily around the scene, but he could never grasp the full meaning of the picture because it was visually scanned in such a piecemeal way. SIMULTANAGNOSIA Patients are not able to perceive more than one object at the time. The ability to perceive single elements in a complex scene, but not the whole image.  Ventral form: patients are not able to distinguish the single elements.  Dorsal form: patients are able to distinguish the single elements but not the whole picture. Dorsal Ventral Patients with simultanagnosia lose the Navon effect: global features are perceived more quickly than local features.  GERSTMANN’S SYNDROME Another syndrome that includes visuo-perceptive deficits. Patients cannot recognize things, cannot write, calculate and recognize left and right:  Finger agnosia.  Agraphia (sometimes + alexia).  Acalculia.  Left/right disorientation. It’s associated with a lesion in the left angular gyrus (inferior parietal lobe) in the dominant hemisphere due to stroke, tumors, multiple sclerosis. There is not a cure for Gerstmann’s Syndrome, but only symptomatic and supportive treatment. Sometimes, symptoms diminish over time.  LANGUAGE AND SPEECH RELATED DISORDERS COMMUNICATION AND LANGUAGE Animals use several modalities to communicate, such as sounds or gestures. Communication in humans is highly related to verbal language. Language is not a synonym of communication. Only humans communicate through arbitrary/conventional symbols, which are different between populations and in constant evolution. Language includes the whole set of these conventional signals and the rules to combine them. The complexity and sophistication of human language suggests that extensive regions of the brain must be dedicated to dealing with it. Any communicative act through language implies:  A sender -> encoding of a message in a linguistic sequence.  A receiver -> decoding of the message, understanding the meaning. Language production and language comprehension. HEMISPHERIC DOMINANCE The two cerebral hemispheres (left and right) do not necessarily participate equally in each cognitive function. As for manual preference, the dominance of the left hemisphere for language is genetically programmed. The concept of dominance does not imply that one hemisphere governs the other, nor that one hemisphere presides exclusively over single integrative functions. Language is mediated by a series of interconnected regions in the left hemi-sphere. This pattern of “distributed control” is found in almost all right-handers, and the majority of left-handers. The right hemisphere:  Understands words and short sentences.  Deciphers written language.  Weak capacity for retaining the auditory messages.  Does not have access to the expressive faculty.  Responsible for knowledge of social concepts and interpretation and use of prosody (emotionally intoned speech) -> patients with right hemisphere disorders may lose the ability to comprehend and show emotion (empathy and embarrassment), interpret sarcasm, and manipulate prosody.  Understanding the non-literal aspects of language, such as metaphors. The recognition of distant semantic and conceptual relations. Perysilvian lesions that cause aphasia are usually located in the left hemisphere in almost all right-handed people and approximately 70% of left-handed or ambidextrous people. In a small % of right-handed people (between 1% and 5%), aphasia may be due to a right hemispheric lesion.  APHASIA Aphasia: general term meaning disruption/loss of language function. Syndrome: a number of symptoms co-occurring and characterizing a particular disease. The mechanistic reason for their co-occurrence is not always fully understood. Aphasic syndrome: a disorder in language production and/or comprehension (which can be differently affected) following a brain lesion, in patients with fully acquired language skills. The deficits cannot be due to the inability to produce linguistic sounds (deficits in the phono-articulatory apparatus), perceive linguistic sounds (deafness) or mental confusion / disorientation / delusion. Aetiology: set of causes of a disease or condition. In aphasia, 40% follow a stroke condition, but it can be present also in degenerative disorders (Alzheimer’s and Pick’s diseases), or related to brain inflammation, tumor or head injury. CLASSICAL APHASIC SYNDROMES BROCA’S APHASIA The core feature is a marked difficulty in producing coherent speech. Difficulties in language production and articulation, especially of novel utterances. Most Broca’s aphasic patients can speak a little, but they seem to have problems in finding the words they want to use, and prepositions, conjunctions, and other relational words are often omitted. As a result, speech is slow, effortful, non-fluent, and deliberate, and may have only a very simple grammatical structure. AGRAMMATISM -> the widespread omission of function words (articles, prepositions, auxiliary verbs) and inflections (adding “-ed” or “ing” to a verb to change its tense, adding “s” to a noun to make it plural, using correct pronouns) coupled with a retention of content words (nouns and non-conjugated verbs). It is also present a speech programming deficit: loss of the ability to execute speech movements (no facial or vocal muscle paralysis). The term “telegraphic speech” has often been used as a short-hand description for Broca’s aphasia speech. Despite these problems, some aspects of language function are well preserved. Patients may be able to sing a well-known song faultlessly, or reading aloud may be relatively unaffected, and usually have preserved comprehension. Most Broca’s patients are aware of their own language difficulties and have “insight” into their condition. The disorder is not related to the “mechanics” of moving the muscles that are concerned with speech. Patient “Tan-Tan” had an impaired language production but spared comprehension. He had a lesion in the left inferior frontal gyrus.  WERNICKE’S APHASIA The problems for Wernicke’s aphasia are related to comprehension, repetition, naming and meaningful output rather than the agrammatical and telegraphic output seen in Broca’s. The core feature is a marked by fluent but nonsensical speech. Two main characteristics:  The patient’s use of non-words (a sequence of letters or sounds that is not accepted as a word by speakers of a specific language) or made-up words.  The use of “paraphasia”: words that are semantically related to the desired word, but nevertheless inappropriate.  Impaired comprehension. This speech is called “word salad” because it tends to include random words and phrases thrown together. Wernicke hypothesized a damage in the “storehouse of auditory word forms” and by analyzing the autopsy of a patient showing similar symptoms he supposed that this storehouse could be located in the posterior part of the superior temporal gyrus (STG). Most Wernicke’s aphasic patients also have little or no “insight” into their condition. They talk nonsense without realizing it, being unaware that other people cannot understand them. In patients we can also observe:  Semantic paraphasias.  PARAGRAMMATISM -> the inability to form grammatically correct sentences. Well-constructed sentences with errors in grammatical morphemes and substitution of lexical items are formed.  Anosognosia. ARCUATE FASCICULUS Language depends on a system, including:  A storehouse (long-term store) of auditory images of words. Lesion in Superior Temporal gyrus -> Wernicke’s aphasia.  A storehouse of motor images of words. Lesion in Inferior Frontal gyrus -> Broca’s aphasia. These systems are connected through the Arcuate fasciculus. ANATOMO-FUNCTIONAL CORRELATION ANATOMO-FUNCTIONAL DOUBLE DISSOCIATION WERNICKE-LICHTHEIM MODEL Connectionist model of language to explain the various forms of aphasia. M -> Motor center: storehouse/center for motor representation of words. A -> Auditory center: storehouse/center for auditory representation of words. B -> Concept center: conceptual representations. Where word meanings are stored and where auditory comprehension occurs. Each point is interconnected, so that damage, either to one of the centers (points), or to any of the pathways connecting them, would induce some form of aphasia. SUBCORTICAL MOTOR APHASIA Pure motor speech disorder: disturbance of articulation, apraxia of speech, inability to program articulatory movements. SUBCORTICAL SENSORY APHASIA Pure word deafness: disturbance of spoken word comprehension; repetition often impaired. Inability to analyze and discriminate (perceive) speech sounds. WHITE MATTER APHASIAS: white matter disconnections. TRANSCORTICAL MOTOR APHASIA Similar to Broca’s aphasia but with preserved repetition and spontaneous speech is absent. More related to muscles. Presence of echolalia (repeat things aloud). TRANSCORTICAL SENSORY APHASIA Impaired comprehension, preserved repetition and spontaneous speech. Presence of echolalia (repeat things aloud). CONDUCTION APHASIA Preserved comprehension, impaired repetition. Disconnection between Broca’s and Wernicke’s area. The frequency of phonological errors in conduction aphasic patients depends on the posterior extension of the lesion, that is, how much it affects: the posterior part of the superior temporal gyrus (BA 22) and the neighbor posterior parietal cortex (supramarginal gyrus, BA 40); or the white matter connecting it to frontal regions (arcuate fasciculus). ANOMIC APHASIA Disturbance in the production of single words, most marked for common nouns. Intact comprehension and repetition. GLOBAL APHASIA Major disturbance in all language functions. Unable to produce, repeat and understand. ISOLATION OF THE LANGUAGE ZONE Disturbance of both spontaneous speech and comprehension, with some preservation of repetition. Disconnection between concepts and both representations of word sounds and the speech production mechanism. LIMITS OF THE CLASSICAL APHASIC SYNDROMES CLASSIFICATION  Most aphasic patients show deficits in both language comprehension and language production, while the model implies a dichotomy -> this is partially replaced by the classification in fluent vs. non-fluent aphasia forms, two qualitatively different speech *.  The association between symptoms and lesions is not so reliable; the brain regions involved in language are much more than those identified by the classical Wernicke-Lichtheim model.  The classification does not consider the analysis of deficits in the different areas of linguistics (phonological, morphological, lexical, syntactic level), which allows a better classification of symptoms and their co-occurrence.  The model does not explain the pattern of dissociations found in aphasic patients; such as the dissociations between deficits in different grammatical classes (nouns, verbs…) or lexical categories.  The model does not allow explaining the behavior of some aphasic patients in tasks like reading and writing or repetition of non-words.  The model does not provide the possibility of processing non-lexical sequences (non-words). * FLUENT APHASIA (Wernkicke’s and Conduction aphasia) No articulatory deficits nor effortful speech; no agrammatism (but paragrammatism). Smooth and abundant speech, long sentences but possible phonological errors, neologisms (phonological deficits) and semantic errors and anomie (semantico-lexical deficits). NON-FLUENT APHASIA (Broca’s and Global aphasia) Possible presence of articulatory deficits and agrammatism. Short sentences, reduced speech.  PSYCHOLINGUISTIC APPROACH Psycholinguistics is the study of the structure of language in normal individuals, and of the psychological/cognitive processes at the basis of language. It studies the interrelation between linguistic factors and psychological aspects; and it concerns the mechanisms by which language is processed and represented in the mind and the brain (neurolinguistics). Psycholinguistics and neurolinguistics study the psychological and neurobiological factors that enable humans to acquire, use, comprehend, and produce language. Linguistics is the scientific study of language and its manifestations. Language is hierarchically organized: 1. Phonetics studies how humans produce and perceive sounds. 2. Phonology studies how languages/dialects systematically organize their sounds in words. Phonological units are the distinctive units that allow the identification of words. Composed by: - Articulatory phonetics = how speech sounds are produced. - Auditory phonetics = classification of speech sounds based on how they are perceived. - Phonetic tracts = how sounds are produced by the phono-articulatory apparatus and perceived by the auditory one. 3. Morphology describes the rules applied to combine phonemes in words. Morphemes are the elementary units of words conveying information. Some morphemes combine to create words (ex. prefix [sub-, pre-, anti-]). 4. Syntax describes the rules applied to combine words in sentences. 5. Semantics describes the association between words and meaning. 6. Grammar describes the rules to combine units in hierarchical structures. 7. Pragmatics studies the language in a context, how it is used in social interactions. CLASSIFICATION OF LANGUAGE SOUNDS Vowels: speech sounds produced by an open configuration of the vocal tract, with vibration of the vocal cords but without audible friction (no obstacles in the flux of air), see a, e, i, o, u, y. Consonants: speech sounds articulated with complete or partial closure, obstruction, of the vocal tract. Consonants are either: o Voiced consonants are pronounced with the same vocal murmur, the vibration of the vocal cords, that is heard in vowels (ex. b, d, g, l, r, m, n, z). o Voiceless consonants are produced without a vibration of the vocal cords and lack this murmur (ex. p, t, c (k, q), f, h, s, x). Consonants can be also classified depending on the place of articulation -> where in the vocal tract the obstruction of the consonant occurs, and which speech organs are involved. For example, bilabial consonants involve both lips, velar consonants involve the tongue against soft palate.  PHONETICS AND PHONOLOGY PHONOLOGICAL SELECTION ERRORS (PRODUCTION) Result in the production of incorrect phonemic sequences, easily recognizable when they constitute neologisms. The patient has problems producing sounds on phoneme level, which is always close to their mother tongue. They include the specific sounds of the patient’s language. Phoneme perception is categorical: we can primarily distinguish, and systematically produce, the speech sounds that we have learnt through linguistic development (mother tongue). Once these categorical boundaries are learnt, they cannot be forgotten. The neologisms follow the same phonemic rules of the patient’s language. PHONOLOGICAL PROCESSING ERRORS Verbal stereotypy: non-propositional utterance characterized by repetition of a syllable, word, or phrase (ex. patient Tan-Tan), typically used in high frequencies and as emotional exclamations. In aphasic patients, a phonological deficit is characterized by the presence of phonemic paraphasia: substitutions, omissions, additions, and transpositions of phonetic units. Phonemic paraphasia refers to the substitution of a word with a word or a nonword that preserves at least half of the segments and/or number of syllables of the intended word. Sometimes these are multiple and make the target words unrecognizable (phonetic neologisms). Some examples of phonemic paraphasia: - Anticipatory errors: a syllable from later in the word replaces a syllable from earlier in the word → "papple" for apple or "lelephone" for telephone. - Paradigmatic errors: based on similarity in how the sounds are formed → "marmer" for barber → lips-related consonants. - Substitution errors: involve a clear phonological substitution → "ragon" for wagon. - Epenthetic errors: the insertion of a segment into the target → "plants" for pants. - Metathetical errors: the full exchange of segments → "deks" for desk. Conduites d’approche: often the patient tries to correct the phonemic errors produced by means of spontaneous corrections, sometimes repeated in trials. In some cases, the phonemic errors can result in words that actually exist and thus simulate a lexical rather than phonological substitution. PHONOLOGICAL DECODING (COMPREHENSION) When listening to spoken words. Frequency effect: higher frequency phonemes and phonological sequences are more easily identified. Lexical status: real versus non-words. People make more errors when listening to non-words than words and tend to interpret acoustically ambiguous phonemes in the form that is semantically congruent.  MORPHO-SYNTACTIC ASPECTS Morphemes are the elementary units of words conveying information; some morphemes combine to create words; and words combine to create sentences. Sentences convey relationships between the meaning of words: Morpho-syntactic aspects are the set of the propositional content of a sentence. Studies in this domain aim to explain why patients make morphological, syntactic, or morphosyntactic errors in language production and comprehension. Morphology describes the class of each word (noun, pronoun, verb, adjective, preposition…), and how to conjugate verbs and create derivations, which is the formation of a word by changing the form of the base or by adding affixes/suffixes to it. Syntax describes the order of the words, how to organize subordinates (dependent), and how to use functional words, such as pronouns (you, them), modal verbs (could, must), determiners (a, the), prepositions (of, in), and conjunctions (and, but). Morpho-syntax describes the relationship between morphology and syntax, such as the rules applied to achieve agreement between nouns and verbs. DISORDERS Propositional content of a sentence: sentences convey relationships between the meaning of words. Syntactic structures describe how individual words can be arbitrarily combined to convey propositional content, to express one of several equally likely relations. Approximately 85% of aphasic patients have troubles in understanding/use the syntactic structure to convey/determine sentence meaning. Patients with Broca’s aphasia show more errors in understanding sentences with reversable roles, where semantics cannot “help”, and the syntactic structure is the only source of information. Aphasic disturbances can affect:  The production of grammatical vocabulary elements -> agrammatism and paragrammatism.  The ability to generate syntactic forms -> impoverishment of syntactic structures in spontaneous speech (simplification).  The ability to assign thematic roles (severely affected patients). SYNTACTIC STRUCTURES They are studied by linguistics as syntactic trees, which establish rules to describe how meaning can be derived from syntactic structures. These are useful for the identification of thematic roles: who does what; and crucial for understanding co-reference (pronouns, reflexives), passive sentences… Deficits in syntactic comprehension and production often co-occur in agrammatic patients, but they can also dissociate, and the severity of the deficit does not correlate. They do not appear to depend on a single functional impairment. Syntactic processing involves the whole left perisylvian associative cortex: - Inferior frontal gyrus (BA 45, 44). - Angular gyrus (BA 39). - Supramarginal gyrus (BA 40). - Superior temporal gyrus (BA 22). LEXICO-SEMANTIC PROCESSING Lexical semantics is the branch of linguistics concerned with the systematic study of word meanings. Lexicon refers to the store of language labels associated with concepts. Semantic lexicons are made up of lexical entries: semantic (not orthographic) and interconnected with semantic relations. Nevertheless, deficits in the semantic system or in the lexical retrieval (lexicon) lead to similar behaviors. The organization of lexicon has been studied by psycholinguistics using computational modelling, an artificial systems mimicking the behavior of patients and healthy subjects, which provide hypotheses on the organization of both the cognitive and the neural systems (artificial neural networks). Phonological input lexicon: translates acoustic to semantic representations. Understanding of the meaning of words. Phonological output lexicon: translates a concept into a spoken word. Word frequency: more frequent words have more connections (more features in common) with other words. These are more resistant, less prone to errors. Age of acquisition: words that are acquired earlier in development are more resistant. During early learning, connection strength changes are large, then they become smaller as the knowledge accumulates. LEXICO-SEMANTIC ERRORS  Anomia: difficulty in retrieving words.  Anomic latency: in the case of a simple delay in recalling a target word. The words not recalled can sometimes be replaced by circumlocutions.  Error in the choice of words, for which there are substitutions with terms of similar meaning (semantic paraphasia; for example: “glass” for “bottle”) or with words without a relation of meaning (verbal paraphasia; for example: “tablecloth” for “telephone”).  Paraphasia: confusions of words or the replacement of one word by another real word. Length of the word is not often preserved. - Categorial: same category -> tiger for lion, car for van. - Associative: replace the target word with one that is related to the target but is not of the same category -> foot with shoe. - Superordinate: replace a specific target word with a more generalized group to which the target word involves -> pear with fruit. - Subordinate: replace the target word with one that is more specific -> rose for flower. DOUBLE DISSOCIATION CATEGORY-SPECIFIC DEFICITS Natural objects (dog, tree, strawberry, …) → left inferior temporal lesions. Artificial objects (comb, scissors, iron, …) → left parietal lesions. Two hypotheses regarding why some patients can/cannot produce one of the previous ones:  Separate organization at lexical output level.  Different organization of conceptual knowledges. Natural objects have visual representations (left occipito-temporal cortex), artificial objects have functional representation (left parietal cortex). GRAMMATICAL CLASSES Noun → intermediate part of the second temporal gyrus versus. Verbs → left premotor frontal lesions for non-fluent aphasia; left posterior temporal and inferior parietal lesions for fluent aphasia. Two hypotheses:  Noun and verbs have different relative weight of perceptual features; verbs have less sensory information.  Based on a peripheral lexical level, where lexical labels are represented separately.  TEST A PATIENT WITH LANGUAGE IMPAIRMENT General medical history and history of language  Left-handed or right-handed.  Bilingual.  Reading and writing.  Evolution of the linguistic disorder. Spontaneous speech (during the clinical interview) The general ability to interact and communicate is tested while asking the patient to provide details related to pathology, disturbances, family situation, habits… It allows evaluating:  The speech content: is it informative?  The pragmatics: is language appropriate to the situation?  Comprehension: does the patient understand my questions? During spontaneous speech it is also possible to identify:  Articulatory disturbances.  Phonological, lexical/semantic, morphological, syntactic errors.  Perseverations and automatisms (ex. repetition of brief lexical idiosyncratic sequences or even meaningless syllables). Systematic evaluation of language abilities in the different areas (phonological, lexical/semantic, morphological, syntactic errors). Object naming or object picture test to assess lexical retrieval ability. This is useful to assess a possible presence of anomia, anomic latency, circumlocutions. Generally, the non-retrieved word is not lost at all; it is not accessible to the patient at that moment, but it can be facilitated through more automatic sentences or expressions, or be found on other occasions. Repetition tasks To assess a possible phonemic paraphasia, phonemic neologisms and conduites d'approche. To test repetition ability, stimuli of different length and complexity are used: starting with bisyllabic words with a simple structure (alternation consonant-vowel) and continues with progressively longer and more complex words and sentences. Oral comprehension 1. Execution of verbal orders: it is best to avoid the most obvious ones, which are part of a medical examination and can get randomly correct answers (ex. "Open your mouth"); it is more appropriate to give "artificial" orders (ex. "Knock the table three times"), to be sure that the patient has actually recognized and understood the command. 2. Recognition of objects: the patient is presented with a series of common objects; the examiner names one and asks the patient to indicate it (ex. "What is the key?", "What is the pen?"). 3. Repetition of words and phrases, said by the examiner.  TREATMENT In the different phases of stroke and related aphasia disorder (acute - chronic), a different therapeutic approach is suitable due to the different neurophysiological mechanisms underpinning each phase. Behavioral protocols for Speech and Language therapies:  Phono-motor treatment: aims to boost word retrieval through the training of phonological skills. Multimodal approach: use of mirror, mouth pictures, written representations… Training starts with single phonemes and gradually progresses to phoneme sequences in nonwords and real words.  Semantic Feature Analysis: lexical retrieval is supported by strengthening semantic networks. Use of feature analysis charts that provide information regarding use, location, physical properties, and association concepts to generate semantic features of target concepts.  Verb Network Strengthening Treatment: lexical retrieval, sentence production and discourse are facilitated by working on verbs, which have a central role in semantics and syntax.  Sound Production Treatment: articulatory–kinematic treatment. Incorrectly produced sounds (monosyllabic and polysyllabic words, phrases, sentences) are practiced hierarchically through modeling, repetition, minimal pair contrast, orthographic cuing, integral stimulation (“watch me, listen to me, say it with me”), and articulatory placement instructions.  Treatment of Underlying Forms: based on generative syntax and targets deficits exhibited at the sentence level in people with agrammatic aphasia by training the production of grammatically complex sentences. Use of written cards that have the components of simple active declarative sentences and a picture illustrating the action. After identifying the verb, patients are trained to reorder sentence components to produce more complex sentences.  Constraint-Induced Language Therapy: a treatment approach for expressive language difficulties. Forced use of spoken language and restraint of all other communication modalities (hand gesturing…). It is an intensive approach necessitating massed practice.  Melodic Intonation Therapy: first developed to recruit right hemispheric brain regions related to the awareness of melody and rhythm to improve expressive language in individuals with non-fluent aphasia. It’s based on rhythmic tapping of the left hand that accompanies the production of syllables, and the exaggeration of the natural prosody of speech. Computerized aphasia therapies derived via computers, smartphones, or tablets. These allow for long-term and low-cost therapy options. NIBS (National Institute of Building Sciences):  Upregulate neural activity in perilesional brain areas of the affected hemisphere through excitatory stimulation protocols (high frequency rTMS, can be delivered alone, or anodal tDCS, always associated to a behavioral speech and language therapy). Perilesional regions of the left hemisphere are recruited to subserve the reorganization and gain of language.  Downregulate neural activity in contra-lesional brain regions through inhibitory stimulation protocols (low frequency rTMS or cathodal tDCS). Based on the “interhemispheric competition model”: there exists a mutual and balanced inhibition between the brain hemispheres. Stroke-induced damage to one hemisphere disrupts this balance leading to reduced inhibition from the affected to the unaffected hemisphere. The unaffected hemisphere, in turn, increases its inhibitory signals to the affected hemisphere. This activation in the