Lectures Week 5: Biological Foundations of Mental Health PDF

Week 5: Learning Outcomes By the end of Topic 1 you will be able to: Briefly describe how information is represented and processed in the cerebral cortex Understand the relevance of the association cortex in acquired, developmental and psychiatric disorders Explain how specific learning tasks...

Week 5: Learning Outcomes By the end of Topic 1 you will be able to: Briefly describe how information is represented and processed in the cerebral cortex Understand the relevance of the association cortex in acquired, developmental and psychiatric disorders Explain how specific learning tasks can be used to analyse cognitive function Explain, with examples, how observing humans with selective injuries to the cerebral cortex, resulting from trauma or disorders, have been instrumental in helping us recognise the function of the association areas of the cortex. By the end of Topic 2 you will be able to: Understand the anatomical and chemical organisation of the different nuclei of the basal ganglia Understand how the electrophysiological properties of basal ganglia neurons affect basal ganglia function and dysfunction Critically evaluate the knowledge gained from studying motor diseases Discuss the role of the basal ganglia in behaviour By the end of Topic 3 you will be able to: Understand how the reward system shapes our behaviours Describe the networks of neurons and neurotransmitter systems that are part of this system, and how its alteration can cause psychiatric disorders like addiction or depression Describe experiments that that can be carried out to study the reward pathway in the living human brain  22/07/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Professor Module: Francesca Happé Biological Foundations of Mental Health Topic 1: Week 5: Reward, emotion and action Cerebral cortex and mental health - Part 1 of 3 Topic list This week, we will be looking at the following topics: Topic 1: Cerebral cortex and mental health Topic 2: The structure and function of the basal ganglia Topic 3: The reward system of the brain Click Next to continue Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 2 of 9 1  22/07/2019 Part 1 Part 1 Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 3 of 9 Overview In this topic, we will look at: - the function of the association cortex and specifically - the frontal lobes high-order control functions - the vital role of the - frontal lobes and what happens when they are affected by acquired or neurodevelopmental disorders - Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 4 of 9 2  22/07/2019 & Areas of the brain primary motor areas secondary primary sensorimotor areas sensory association cortex association cortex We will focus on the functions of the association cortex and the relevance of this part of the brain for understanding acquired, basal ganglia thalamus developmental, and psychiatric disorders. association hippocampus cortex brain stem cerebellum Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 5 of 9 Top-down effects on perception The association cortex integrates sensory and motor information to produce a meaningful perception of the world around us, as well as allowing for abstract representation and flexible behaviour. Porter (1954) Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 6 of 9 3  22/07/2019 Subdivisions of the association cortex-down effects on perception The association cortex can be divided into three: Posterior or parietal association area Anterior or frontal Responsible for: association area Attention, convergence of Responsible for: visual, auditory and Planning, decision making somatosensory information and working memory Abnormal functioning of the frontal lobes and especially the prefrontal cortex are believed to be the cause of many psychiatric and neurodevelopmental conditions. Limbic or temporal association area Responsible for: Long term memory and emotional responses Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 7 of 9 Executive functions Executive functions are especially important when we are faced with novel situations or challenges. Cortex. ↳ Fo Generating Planning Monitoring Switching Inhibiting behaviour Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 8 of 9 4  22/07/2019 End of part 1 End of part 1 Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 9 of 9 5  22/07/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Professor Module: Francesca Happé Biological Foundations of Mental Health Topic 1: Week 5: Cerebral cortex and Reward, emotion and action mental health Part 2 of 3 Part 2 Part 2 Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 2 of 7 1  22/07/2019 Wisconsin card sort test - Wrong Correct Correct Correct Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 3 of 7 Tower of Hanoi - Hover over the video and press play to rewatch the video. Click Next to continue Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 4 of 7 2  22/07/2019 Stroop task Fr RED GREEN BLUE PURPLE PURPLE RED GREEN YELLOW YELLOW GREEN RED PURPLE GREEN BLUE PURPLE YELLOW Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 5 of 7 N-back task a Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 6 of 7 3  22/07/2019 End of part 2 End of part 2 Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 7 of 7 4  22/07/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Professor Module: Francesca Happé Biological Foundations of Mental Health Topic 1: Week 5: Cerebral cortex and Reward, emotion and action mental health Part 3 of 3 Part 3 Part 3 Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 2 of 17 1  22/07/2019 Introduction to part 3 Executive functions There are at least two - sources of evidence: * Neuroimaging, e.g. fMRI *Neuropsychological studies of acquired brain damage to frontal lobes Frontal cortex = Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 3 of 17 Functional Magnetic Resonance Imaging (fMRI) - fMRI studies show how blood flow changes in the prefrontal regions of the brain when volunteers engage in cognitive tasks. Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 4 of 17 2  22/07/2019 Activation in frontal regions is greatest for novel tasks and decreases with practice Hampshire and colleagues Findings: (2016) Activation in the frontal regions decreases across the blocks of an inhibition task as the New skill volunteers become more practised at the test. Frontal brain regions Hampshire et al. (2016) Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 5 of 17 Cases of acquired frontal lobe damage Another source of evidence for the role of the frontal regions of the brain in executive functions comes from The case of neuropsychological cases of acquired brain damage. Phineas Gage The case of Phineas Gage “The damage to Gage’s frontal cortex caused by the iron rod seems to have resulted in a loss of social inhibitions. The role of the frontal cortex in social cognition and decision making is now well-recognised; in the 19th century, however, neurologists were only just beginning to realise these connections. Gage’s injuries provided some of the first evidence that the frontal cortex was involved in personality and behaviour.” For more information on the case of Phineas Gage, please see the Consolidation and Reflection section. Click Next to continue BigPicture (2017); Costandi (2012); Harlow (1993, 1999); Van Horn et al. (2012) Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 6 of 17 3  22/07/2019 Frontal association cortex implicated in many psychiatric and neurodevelopmental conditions - Autism spectrum disorder (ASD) - * Several psychiatric and - neurodevelopmental conditions Schizophrenia are associated with an impairment in executive functions, such as: Bipolar disorder Major depression Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 7 of 17 Autism Spectrum Disorder (ASD) - Autism spectrum disorder (ASD) is characterised by: impaired social and communicative development rigid and repetitive behaviours and interests Frontal lobes poor performance on executive function tasks Especifically a dislike for change a preference for narrow routines and repetition planning/ shiffy taats(wisconsis Topic 1: Cerebral cortex andWeek fast Week 5 Reward, emotion and action 2 –health mental Lorem ipsum 8 of 17. 4  22/07/2019 Social and communication problems in ASD reflect impaired ‘Theory of Mind’ - D ‘Theory of mind’: The ability to recognise others’ thoughts, beliefs and desires, putting yourself in another person’s shoes. - - - * People with ASD tend to have difficulty * They often get confused by social situations understanding what others are thinking. and struggle with communication. Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 9 of 17 A simple test of ‘Theory of Mind’: The Frith-Happé triangles animations - Hover over the video and press play to rewatch the first animation. Click Next to continue Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 10 of 17 5  22/07/2019 A simple test of ‘Theory of Mind’: The Frith-Happé triangles animations - Hover over the videos and press play to rewatch the second and third animations. Click Next to continue Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 11 of 17 &AD Theory of mind tasks - dont attribute thosets in trianyls-- Blakemore and Decety, 2001 Castelli and colleagues, 2002 - - fMRI results during ‘Theory of Mind’ animations task Extra-striate Basal Superior Medial cortex Temporal Temporal Sulcus Prefrontal The Frith-Happé triangles animations - 10 autistic 10 control Blakemore & Decety (2001); Castelli et al. (2002) Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 12 of 17 6  22/07/2019 Fact other objects especially v. ~ Reduced ‘top-down’ effects in ASD - Loth and colleagues, 2010 Brain scans suggest a reduced top-down effect in people with ASD. ASC: Autism Spectrum Conditions TD: Typically Developing adults Loth et al. (2010) Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 13 of 17 - ahpice. Connectivity differences in ASD - Take your time to study the images on the slide. Click Next to continue Ha et al. (2015) Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 14 of 17 7  22/07/2019 Conclusion - We have looked at: - the association cortex - the role of the frontal lobes in executive functions all acquired or developmental abnormalities in these regions and the consequent impairment in responding flexibly to novel situations the hypothesis on the importance of the frontal lobes in many psychiatric and neurodevelopmental disorders - Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 15 of 17 References BigPicture. (2017). Brain case study: Phineas Gage [webpage]. Retrieved from https://bigpictureeducation.com/brain-case-study-phineas-gage Blakemore, S. J., & Decety, J. (2001). From the perception of action to the understanding of intention. Nature Reviews Neuroscience, 2(8), 561. Castelli, F., Frith, C., Happé, F., & Frith, U. (2002). Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain, 125(8), 1839-1849. Costandi, M. (2012). Phineas Gage's connectome [article]. Retrieved from https://www.theguardian.com/science/neurophilosophy/2012/may/16/neuroscience-psychology Ha, S., Sohn, I. J., Kim, N., Sim, H. J., & Cheon, K. A. (2015). Characteristics of brains in autism spectrum disorder: structure, function and connectivity across the lifespan. Experimental Neurobiology, 24(4), 273-284. Hampshire, A., Hellyer, P. J., Parkin, B., Hiebert, N., MacDonald, P., Owen, A. M.,... & Rowe, J. (2016). Network mechanisms of intentional learning. Neuroimage, 127, 123-134. Harlow, J. M. (1993). Recovery from the passage of an iron bar through the head. History of Psychiatry, 4(14), 274-281. Harlow, J. M. (1999). Passage of an iron rod through the head. The Journal of Neuropsychiatry and Clinical Neurosciences, 11(2), 281-283. Loth, E., Gómez, J. C., & Happé, F. (2010). When seeing depends on knowing: adults with autism spectrum conditions show diminished top-down processes in the visual perception of degraded faces but not degraded objects. Neuropsychologia, 48(5), 1227-1236. Porter, P. B. (1954). Another picture puzzle. American Journal of Psychology, 67, 550-551. Van Horn, J. D., Irimia, A., Torgerson, C. M., Chambers, M. C., Kikinis, R., & Toga, A. W. (2012). Mapping connectivity damage in the case of Phineas Gage. PloS One, 7(5), e37454. Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 16 of 17 8  22/07/2019 Attributions Bussu, G. (2015). Attentional Modulation Effects on Brain Networks: an fMRI Study on the Visual Attention Network and the Default-Mode Network. Sapienza, Universita di Roma. Retrieved from https://www.researchgate.net/figure/The-cerebral-cortex-is-morphologically-divided-into-lobes-by-deep-fissures-frontal_fig9_281239686 Database Center for Life Science (DBCLS) / Polygon data is from BodyParts3D. (2015). Phineas Gage injury - lateral view (frontal lobe) [image]. Retrieved from https://commons.wikimedia.org/w/index.php?curid=44466317 Encyclopaedia Britannica, Inc. (2019). Functional areas of the human brain [image]. Retrieved from http://www.britannica.com/science/human-nervous-system/Lobes-of-the- cerebral-cortex Harlow, J. M. (1868). Skull diagram of Phineas Gage [image]. Retrieved from https://commons.wikimedia.org/w/index.php?curid=2969748 Insituto Balseiro. (n.d.). How Are Qualia Localized in Consciousness? [image]. Retrieved from http://cogsci.stackexchange.com/questions/2048/how-are-qualia-localized-in- consciousness Ratiu, P., Talos, I. F., Haker, S., Lieberman, D., & Everett, P. (2004). The tale of Phineas Gage, digitally remastered. Journal of Neurotrauma, 21(5), 637-643. Vandyke Carter, H., Gray, H. (1918). Anatomy of the Human Body (See "Book" section below) Bartleby.com: Gray's Anatomy, Plate 728 [image]. Retrieved from https://commons.wikimedia.org/w/index.php?curid=541548 Wilgus, J and B / Warren Anatomical Museum, Center for the History of Medicine, Francis A. Countway Library of Medicine, Harvard Medical School. (2009). Photograph of cased-daguerreotype studio portrait of brain-injury survivor Phineas P. Gage (1823–1860) [image]. Retrieved from https://commons.wikimedia.org/w/index.php?curid=64865123 Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 17 of 17 End of topic End of topic Week 5 Reward, emotion and action Topic 1: Cerebral cortex andWeek 2 –health mental Lorem ipsum 18 of 17 9  Module: Biological Foundations of Mental Health Week 5 Biological basis of learning, memory & cognition Topic 1 Cerebral cortex and mental health - Part 3 of 3 Professor Francesca Happé Professor of Cognitive Neuroscience, Institute of Psychiatry, Psychology and Neuroscience Lecture transcript Slide 3 How do we know that the frontal cortex is important for executive functions? There are at least two sorts of evidence, neuroimaging and neuropsychological cases of acquired frontal lobe damage. Slide 4 fMRI studies show prefrontal regions are active when volunteers engage in tasks, like those you just tried, the Wisconsin card sorting test, the Tower of Hanoi, the Stroop task, and the N-back task. Slide 5 Interestingly, frontal regions seem to be particularly important when we’re learning new skills. Once environment, frontal regions are essential. This is illustrated in a study by Hampshire, et al., 2015. See how the activation in the frontal regions decreases across the blocks of an inhibition task as the volunteers become more practised at the test. Slide 6 The second source of evidence for the importance of the frontal lobes in executive functions comes from neuropsychological cases of acquired brain damage. When previously healthy people have a head injury or a stroke that damages their frontal lobes, they typically show impairments in judgement and decision-making. Slide 7 A range of psychiatric and neurodevelopmental conditions are also associated with impairments in executive functions and frontal lobe integrity. Autism spectrum disorder, schizophrenia, bipolar Slide 8 Let’s look more closely at autism as an example of a neurodevelopmental disorder where the frontal lobes are implicated. Transcripts by 3Playmedia Week 5 © King’s College London 2019 1.  Autism spectrum disorder, or ASD, is a neurodevelopmental condition characterised by impaired social and communicative development, with rigid and repetitive behaviours and interests. Children and adults with ASD show impairment in executive functions, particularly on planning tasks, like the Tower of Hanoi, and set-shifting, like the Wisconsin card sorting test. Most children and adults with ASD dislike change and have a strong preference for narrow routines and repetition. This is thought novelty. Slide 9 from an impairment in recognising what others are thinking, so-called “theory of mind.” Because by social situations and struggle with communication. Think how confusing it would be to be told to “paint the child next to you” if you couldn’t guess what the teacher meant. Slide 10 Theory of mind can be tested with a variety of tasks. Watch the following short animation. Slide 11 What does the small triangle want? What is the big triangle trying to do? Let’s look at some more examples. Slide 12 Using animations like these, or static cartoons or written stories that also cause healthy volunteers to think about other people’s thoughts, fMRI studies show activation of medial prefrontal cortex, as well as temporal poles and superior temporal sulcus. People with ASD often simply see triangles moving around and don’t attribute thoughts to them. Asked what was going on in the animations, they might say the red one moved right and then the blue one turned 90 degrees. The brain activity of questions correctly. Slide 13 Remember how seeing the picture of the face helped you see the blobs as a face? People with objects. Slide 14 Unlike acquired frontal lobe patients, people with ASD do not have circumscribed lesions. Instead, it Slide 15 In this session we have looked at the association cortex and focused especially on the frontal lobes and their role in executive functions. Acquired or developmental abnormalities in these regions impair frontal involvement is hypothesised to underlie many psychiatric and neurodevelopmental symptoms. Transcripts by 3Playmedia Week 5 © King’s College London 2019 2.  Module: Biological Foundations of Mental Health Week 5 Biological basis of learning, memory & cognition Topic 1 Cerebral cortex and mental health - Part 1 of 3 Professor Francesca Happé Professor of Cognitive Neuroscience, Institute of Psychiatry, Psychology and Neuroscience Lecture transcript Slide 4 In previous topics, you have learned about the structure of the brain and the sensory and motor the frontal lobes. You will learn about the high-order control functions that allow us to deal with new Slide 5 and motor areas, secondary sensorimotor areas, and association cortices. This topic will focus on the functions of the association cortex and the relevance of this part of the brain for understanding The association cortex takes information from primary and secondary sensory and motor cortices as well as the brain stem and thalamus. It sends information to the cerebellum, basal ganglia, and Slide 6 from primary visual cortex to regions where objects are recognised and named. However, ambiguous stimuli. look at these blobs. Can you see anything meaningful in them? Now have a look at this picture. Here are those blobs again. Do you see what they are now? The blobs haven’t changed, but the top- down information in your brain has. Now your knowledge from the picture helped you complete the perception of the blobs and see them as a face. The association cortex integrates sensory and motor information to produce meaningful perception of the world around us. But it does more than this. It allows abstract representation and supports Transcripts by 3Playmedia Week 5 © King’s College London 2019 1.  Slide 7 The association cortex can be divided into three-- the posterior or parietal association area, the limbic or temporal association area, and the anterior or frontal association area. These association attention and the convergence of sensory information. Here, the visual, auditory, and somatosensory information meets. The limbic association area is involved in forming long-term memories and frontal lobes, including the prefrontal cortex-- is vital for planning, decision making, and working memory. The frontal association area is particularly important for mental health. Many psychiatric and neurodevelopmental conditions are believed to involve abnormal functioning of the frontal lobes, and especially the prefrontal cortex. Slide 8 The frontal cortex plays a vital role in a set of higher-order cognitive processes termed executive behaviour. All these are especially important when we are faced with novel situations or challenges. Think about a time when you have had to cope with change-- for example, if you have a bathroom reach up automatically to where the light pull used to be. Your frontal lobes need to kick in to help you inhibit that now-irrelevant action. Let’s take a closer look at some executive functions and how they are typically tested or measured. Transcripts by 3Playmedia Week 5 © King’s College London 2019 2.  Module: Biological Foundations of Mental Health Week 5 Biological basis of learning, memory & cognition Topic 1 Cerebral cortex and mental health - Part 2 of 3 Professor Francesca Happé Professor of Cognitive Neuroscience, Institute of Psychiatry, Psychology and Neuroscience Lecture transcript Slide 3 In 1948, Grant and Berg published their now very famous Wisconsin Card Sorting Test. It is a test of criteria. You have three ways to classify a card, and the only feedback you get is whether you are the symbols, or the number of the shapes on each card. suddenly the rule changes. Our player now has to decide on which rule to try out. She can choose either shape or number. She chooses number, and again, she is lucky. As you will notice later when you try the game yourself, after the rule changes, you are prone to making more mistakes. The task measures how well people can adapt to the changing rules. Slide 4 The Tower of Hanoi was designed to test your cognitive abilities. The rules of the game are straightforward. You are presented with three pegs and a number of discs stacked up on one of the pegs in order of size, with the biggest disc at the bottom. Your task is to transfer the whole tower one. To do this task, you have to think ahead several moves to make the best decisions. The task tests your ability to plan. Let’s watch as someone plays the game. Slide 5 In this task, you are presented with a number of coloured shapes and are then asked to name the colours as fast as you can from left to right. Once you have completed this task, you are given a similar list. But this time, you are not presented with shapes but rather with coloured words. The trick is that the actual word red, for example, is not necessarily coloured red but blue or some other colour. You are then asked to name the colour the word is printed in as opposed to the colour the word spells out. Why not try it for yourself? Transcripts by 3Playmedia Week 5 © King’s College London 2017 1.  You will notice that it is much harder to get the colour right when reading the words, because the generates. So the Stroop task measures inhibitory control. Slide 6 attention and working memory. In the task, you are asked to look at a sequence of objects. In the two-back test, you are asked to respond when you see an object repeated after a sequence of two images have been displayed. In a three-back test, you have to wait until you see the same image after a sequence of three images have been displayed, and so on. Let’s have a look at someone playing the two-back game. The sequence starts, and when our player the image of the cheese repeated. The game will get harder as the player has to hold longer intervals in mind. Recalling three-back is harder than two, and so on. The n-back game tests working memory. That’s the ability to hold information in mind while you manipulate it. Transcripts by 3Playmedia Week 5 © King’s College London 2017 2.  13/06/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Dr Frank Hirth Week 5: Topic 2 The structure and function Reward, emotion and action of the Basal Ganglia Part 1 of 5 * Y Anatomy (1) strictern - - = = - / - ~ Figure 1: Location of basal ganglia in the brain Figure 2: Anatomy of the basal ganglia Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 2 of 16 1  13/06/2019 Anatomy (2) The basal ganglia (BG) consists of an arrangement of basal forebrain nuclei that includes the striatum (which in primates consists of caudate, putamen and ventral striatum, including nucleus accumbens) globus pallidus (GP) which consists of the internal and external domains of the globus pallidus (GPi and GPe, respectively) the subthalamic nucleus (STN), - the substantia nigra pars reticulata (SNr) Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 3 of 16 Anatomy (3) Figure 3: Section through the brain showing the basal ganglia Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 4 of 16 2  13/06/2019 Connectivity (1) pat in - = ↓ Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 5 of 16 Connectivity (2) contentGauhic use -dilt * & R cortice amast diff connectio Figure 4: Sensorimotor, associative and ventral (limbic) loops in mammals, here shown for primates Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 6 of 16 3  13/06/2019 Connectivity (3) -T · - - I Week 5 Reward, emotion and action Redbita rections Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 7 of 16 Connectivity (4) i Input: ▪ Caudate and putamen (together, the striatum) Output: ▪ Substantia nigra pars reticulata (SNr) (Bothe ▪ Internal segment of globus pallidus (GPi) Intrinsic: Neuromodulator: ▪ Subthalamic nucleus (STN) ▪ Substantia nigra pars compacta (SNc) Dopaminesic - ▪ External segment of globus pallidus (GPe) - - SNc ---- ↑ Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 8 of 16 4  13/06/2019 Connectivity (5) Functional topography: Parallel loops within the basal ganglia subserve distinct functions - multiplication : * of exciting Irope that th some functions. Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 9 of 16 Connectivity (6) > - Movement modulation through disinhibition - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 10 of 16 5  13/06/2019 Connectivity (7) Movement modulation through disinhibition - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 11 of 16 Connectivity (8) Output nuclei of the basal ganglia are inhibitory - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 12 of 16 6  13/06/2019 Connectivity (9) -edut Output nuclei maintain a high tonic level of discharge, suppressing activity in target regions > - reaction de Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 13 of 16 Connectivity (10) absenceenement Firing under quiescent conditions of Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 14 of 16 7  13/06/2019 Connectivity (11) Movement modulation occurs through disinhibition of thalamocortical target regions - = & - # - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 15 of 16 Connectivity (12) - Basal Ganglia: Movement modulation through disinhibition 1. Output nuclei of the basal ganglia are inhibitory 2. Output nuclei maintain a high tonic level of discharge, suppressing activity in target regions 3. Phasic decrease in firing rate transiently releases target regions from inhibition. 4. Disinhibited thalamocortical circuit discharges, promoting movement. Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 16 of 16 8  13/06/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Dr Frank Hirth Week 5: Topic 2 The structure and function Reward, emotion and action of the Basal Ganglia Part 2 of 5 Direct and Indirect Pathways (1) - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 2 of 18 1  13/06/2019 Direct and Indirect Pathways (2) Direct Pathway we -Tot pet nai Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 3 of 18 Direct and Indirect Pathways (3) Basal firing rates in the striatum are very low, and dependent upon strong cortical excitation. allexcitations - -apand Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 4 of 18 2  13/06/2019 Direct and Indirect Pathways (4) Under these conditions, striatal firing has little impact on GPi/SNr discharge - Fatim hoeffe- Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 5 of 18 Direct and Indirect Pathways (5) Phasic cortical excitation drives excitatory discharge in the striatum corticultation. Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 6 of 18 3  13/06/2019 Direct and Indirect Pathways (6) Activation of the direct pathway promotes action. port / O This causes a transient inhibition of GPi/SNr firing. Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 7 of 18 Direct and Indirect Pathways (7) Indirect pathway - I ent Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 8 of 18 4  13/06/2019 Direct and Indirect Pathways (8) Striatal neurons have low tonic firing rates; again, dependent upon strong cortical inputs - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 9 of 18 Direct and Indirect Pathways (9) GPe neurons are similar to those in GPi; they have high tonic firing rates = Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 10 of 18 5  13/06/2019 Direct and Indirect Pathways (10) Because of Inhibitory Activity of GPe neurons STN Activity is Suppressed - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 11 of 18 Direct and Indirect Pathways (11) Firing under these quiescent conditions high discharge in output nuclei (GPi/SNr) is maintained and thus thalamus inhibited - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 12 of 18 6  13/06/2019 Direct and Indirect Pathways (12) What happens to indirect pathway with strong, phasic cortical excitation? -- Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 13 of 18 Direct and Indirect Pathways (13) Transient inhibition of GPe firing - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 14 of 18 7  13/06/2019 Direct and Indirect Pathways (14) Followed by phasic excitation of the STN (through disinhibition) - = ter Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 15 of 18 Direct and Indirect Pathways (15) And finally, a increased rate of discharge in the output nuclei because of - excitatory connection between STN and output nuclei - S Activation of the indirect pathway suppresses action - T because of enhanced further invibitieral suppression of thalamus. = - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 16 of 18 8  13/06/2019 Direct and Indirect Pathways (16) Indirect pathway Direct pathway Week 5 S Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 17 of 18 Direct and Indirect Pathways (17) Indirect pathway suppresses action. Direct pathway facilitates action. - - How do they cooperatively regulate motor output? - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the basal2 ganglia – Lorem ipsum 18 of 18 9  13/06/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Dr Frank Hirth Week 5: Topic 2 The structure and function Reward, emotion and action of the Basal Ganglia Part 3 of 5 Dopamine as modulator of the pathways (1) - Dopamine (DA) input arises from the SNc - - Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 2 of 10 1  13/06/2019 Dopamine as modulator of the pathways (2) Direct and Indirect pathways express distinct dopamine receptors - * Because of the different nature of D1 and D2 receptors, they - respond differently to DA > Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 3 of 10 Dopamine as modulator of the pathways (3) D2 signalling suppresses firing in indirect pathway neurons Week 5 Reward, emotion and action Week Topic 2: The structure and function of the Basal2 Ganglia – Lorem ipsum 4 of 10 2  13/06/2019 Dopamine as modulator of the pathways (4) - D2 signalling suppresses firing in indirect pathway neurons * DA acting on D2 reduces the indirect pathways inhibitory effect and thus facilitates movement = Week 5 Reward, emotion and action