Sensorimotor systems Learning, memory & amnesia Chapters 8 and 11

Three principles of sensorimotor function hierarchical organization hierarchical organization Two other organizing characteristics? Two other organizing characteristics? motor output is guided by sensory input motor output is guided by sensory input The case of G.O. – darts champion The case of G.O. – darts champion The exception? The exception? learning changes the nature and locus of sensorimotor control learning changes the nature and locus of sensorimotor control

Posterior Parietal Association Cortex Function: Integrates of sensory information to plan and initiate voluntary movement and attention. Sensory system inputs: visual, auditory and somatosensory. Outputs: dorsolateral PFC, secondary motor cortex and frontal eye fields.

Frontal eye field Dorsolateral PFC Visual cortex Auditory cortex Inputs to Posterior Parietal Association Cortex

Frontal eye field Dorsolateral PFC Visual cortex Auditory cortex Outputs to Posterior Parietal Association Cortex

Damage to the Posterior Parietal Association Cortex Can produce a variety of deficits Attention Attention Perception and memory of spatial relationships Perception and memory of spatial relationships Reaching and grasping Reaching and grasping Control of eye movements Control of eye movements

Damage to the Posterior Parietal Association Cortex Apraxia – a disorder of voluntary movement not attributable to a simple motor deficit (weakness or paralysis) or to a deficit in comprehension or motivation. Results from unilateral damage to the left posterior parietal cortex.

Damage to the Posterior Parietal Association Cortex Contralateral neglect – a disturbance in a patient’s ability to respond to stimuli on the side of the body contralateral to a brain lesion (not a simple sensory or motor deficit). Often associated with large lesions of the right posterior parietal lobe.

Dorsolateral Prefrontal Cortex Function: plays a role in the evaluation of external stimuli and initiation of voluntary responses to those stimuli. Main input: posterior parietal cortex Outputs: secondary motor cortex primary motor cortex frontal eye fields

Dorsolateral Prefrontal connectivity

Dorsolateral Prefrontal cortex Neurons in this area respond to the characteristics of objects (e.g., color/shape), the location of objects or to both. The activity of other neurons is related to the response itself.

Secondary motor cortex Input: most from association cortex Output: primary motor cortex Two classic areas: 1) SMA 2) Premotor cortex

Secondary Motor Cortex Current classifications suggest At least 7 different areas At least 7 different areas 3 supplementary motor areas 3 supplementary motor areas SMA and preSMA and Supplementary eye field SMA and preSMA and Supplementary eye field 2 premotor areas 2 premotor areas PMd and PMv PMd and PMv 3 cingulate motor areas 3 cingulate motor areas CMAr, CMAv and CMAd CMAr, CMAv and CMAd

Secondary Motor Cortex Subject of ongoing research Subject of ongoing research In general, may be involved in programming patterns of movements based on input from PFC In general, may be involved in programming patterns of movements based on input from PFC Mirror neurons – in premotor cortex (also in posterior parietal cortex) are involved in social cognition, theory of mind and may contribute to autism if dysfunctional. Mirror neurons – in premotor cortex (also in posterior parietal cortex) are involved in social cognition, theory of mind and may contribute to autism if dysfunctional.

Primary Motor Cortex Precentral gyrus of the frontal lobe Precentral gyrus of the frontal lobe Major point of convergence of cortical sensorimotor signals Major point of convergence of cortical sensorimotor signals Major point of departure of signals from cortex Major point of departure of signals from cortex Somatotopic – more cortex devoted to body parts which make many movements Somatotopic – more cortex devoted to body parts which make many movements

Motor homunculus

Primary Motor Cortex Monkeys have two hand areas in each hemisphere, one receives feedback from receptors in skin. Monkeys have two hand areas in each hemisphere, one receives feedback from receptors in skin. Stereognosis – recognizing by touch – requires interplay of sensory and motor systems Stereognosis – recognizing by touch – requires interplay of sensory and motor systems Damage to primary motor cortex Damage to primary motor cortex Movement of independent body parts (e.g., 1 finger) Movement of independent body parts (e.g., 1 finger) Astereognosia Astereognosia Speed. accuracy and force of movement Speed. accuracy and force of movement

Other sensorimotor structures outside of the hierarchy (sometimes called extrapyramidal systems) Cerebellum Cerebellum Basal ganglia Basal ganglia both modulate and coordinate the activity of the pyramidal systems by interacting with different levels of the hierarchy.

Cerebellum 10% of brain mass, > 50% of its neurons 10% of brain mass, > 50% of its neurons Converging signals from Converging signals from primary and secondary motor cortex primary and secondary motor cortex brain stem motor nuclei (descending motor signals) brain stem motor nuclei (descending motor signals) Somatosensory and vestibular systems (motor feedback) Somatosensory and vestibular systems (motor feedback) Involved in motor learning, particularly sequences of movement Involved in motor learning, particularly sequences of movement Damage to cerebellum – disrupts direction, force, velocity and amplitude of movements; causes tremor and disturbances of balance, gait, speech, eye movement and motor sequence learning. Damage to cerebellum – disrupts direction, force, velocity and amplitude of movements; causes tremor and disturbances of balance, gait, speech, eye movement and motor sequence learning.

Basal Ganglia A collection of nuclei A collection of nuclei Part of neural loops that receive cortical input and send output back via the thalamus (cortical-basal ganglia-thalamo- cortical loops) Part of neural loops that receive cortical input and send output back via the thalamus (cortical-basal ganglia-thalamo- cortical loops) Modulate motor output and cognitive functions Modulate motor output and cognitive functions Cognitive functions of the basal ganglia Cognitive functions of the basal ganglia

Descending Motor Pathways Two dorsolateral Two dorsolateral Corticospinal Corticospinal Corticorubrospinal Corticorubrospinal Two ventromedial Two ventromedial Corticospinal Corticospinal Cortico-brainstem-spinal tract Cortico-brainstem-spinal tract The corticospinal tracts are direct pathways The corticospinal tracts are direct pathways

Dorsolateral Vs Ventromedial Motor Pathways Ventromedial one direct tract, one that synapses in the brain stem one direct tract, one that synapses in the brain stem More diffuse More diffuse Bilateral innervation Bilateral innervation Proximal muscles Proximal muscles Posture and whole body movement Posture and whole body movementDorsolateral one direct tract, one that synapses in the brain stem one direct tract, one that synapses in the brain stem Terminate in one contralateral spinal segment Terminate in one contralateral spinal segment Distal muscles Distal muscles Limb movements Limb movements

Experiments by Lawrence and Kuypers (1968) Experiment 1: bilateral transection of the Dorsolateral (DL) corticospinal tract Results: 1) monkeys could stand, walk and climb 2) difficulty reaching but improved over time 3) could not move fingers independently of each other or release objects from their grasp.

Experiments by Lawrence and Kuypers (1968) Experiment 2: The same monkeys with DL corticospinal tract lesions received 1 of 2 additional lesions: 1) The other indirect DL tract was transected 2) Both ventromedial (VM) tracts were transected

Experiments by Lawrence and Kuypers (1968) Experiment 2 Results: The DL group could stand, walk and climb but limbs could only be used to ‘rake’ small objects of interest along the floor VM group had severe postural abnormalities: great difficulty walking or sitting. Although they had some use of the arms they could not control their shoulders.

Experiments by Lawrence and Kuypers (1968) Conclusions: the VM tracts are involved in the control of posture and whole-body movements the DL tracts control limb movements (only the direct tract controls independent movements of the digits.

The case of H.M. Intractable epilepsy Intractable epilepsy one generalized convulsion each week one generalized convulsion each week Several partial convulsions each day Several partial convulsions each day 1953 surgery: Bilateral medial temporal lobectomy 1953 surgery: Bilateral medial temporal lobectomy temporal pole temporal pole amygdala amygdala entorhinal cortex entorhinal cortex hippocampus hippocampus

Corkin et al. (1997)

Effects of Bilateral Medial Temporal Lobectomy Convulsions were dramatically reduced Convulsions were dramatically reduced IQ increased from 104 to 118 IQ increased from 104 to 118 Short-term memory (STM) intact Short-term memory (STM) intact Temporally-graded retrograde amnesia Temporally-graded retrograde amnesia Severe anterograde amnesia Severe anterograde amnesia

Amnesia Retrograde (backward-acting) – unable to remember the past Retrograde (backward-acting) – unable to remember the past Anterograde (forward-acting) – unable to form new memories Anterograde (forward-acting) – unable to form new memories While H.M. was unable to form most types of new long-term memories, his STM was intact While H.M. was unable to form most types of new long-term memories, his STM was intact

Mirror-drawing task H.M.’s performance improved over 3 days (10 trials/day) despite the fact that he could not consciously remember the task on days 2 and 3.

Rotary-Pursuit Test H.M.’s performance improved over 9 daily practice sessions; again, with no recognition of the experience

Explicit vs Implicit Memories Explicit memories – conscious memories Explicit memories – conscious memories Implicit memories – unconscious memories Implicit memories – unconscious memories Repetition priming tests were developed to assess implicit memory performance;

Incomplete pictures test

Implications of H.M.’s amnesia Medial temporal lobes are involved in memory formation. Medial temporal lobes are involved in memory formation. STM and LTM are dissociable – H.M. is unable to consolidate certain kinds of explicit memory. STM and LTM are dissociable – H.M. is unable to consolidate certain kinds of explicit memory. the fact that he could form some memories suggests that there are multiple memory systems in the brain. the fact that he could form some memories suggests that there are multiple memory systems in the brain.

Medial Temporal Lobe Amnesia Not all patients with this form of amnesia are unable form new explicit long-term memories, as was the case with H.M. Not all patients with this form of amnesia are unable form new explicit long-term memories, as was the case with H.M. Two kinds of explicit memory: Semantic memory (general information) may function normally while episodic memory (events that one has experienced) does not – they are able to learn facts, but do not remember doing so (the episode when it occurred)

Vargha-Khadem et al., (1997) Studied three children that had bilateral temporal lobe damage early in life. Studied three children that had bilateral temporal lobe damage early in life. Like H.M., the children could not form episodic memory, however they did acquire reasonable levels of factual knowledge and language ability in mainstream school. Like H.M., the children could not form episodic memory, however they did acquire reasonable levels of factual knowledge and language ability in mainstream school.

Effects of Cerebral Ischemia on the Hippocampus and Memory R.B. suffered damage to just one part of the hippocampus (CA1 pyramidal cell layer) and developed amnesia R.B. suffered damage to just one part of the hippocampus (CA1 pyramidal cell layer) and developed amnesia R.B.’s case suggests that hippocampal damage alone can produce amnesia R.B.’s case suggests that hippocampal damage alone can produce amnesia H.M.’s damage and amnesia was more severe than R.B.’s H.M.’s damage and amnesia was more severe than R.B.’s

Object-Recognition Memory Early animal models of amnesia involved implicit memory and assumed the hippocampus was key Early animal models of amnesia involved implicit memory and assumed the hippocampus was key 1970’s – monkeys with bilateral medial temporal lobectomies showed LTM deficits in the delayed nonmatching-to-sample test 1970’s – monkeys with bilateral medial temporal lobectomies showed LTM deficits in the delayed nonmatching-to-sample test Like H.M., performance was normal when memory needed to be held for only a few seconds (within the duration of STM) Like H.M., performance was normal when memory needed to be held for only a few seconds (within the duration of STM)

Delayed nonmatching-to-sample task pretend you’re the monkey Sample stimulus touch it and get a yummy treat

10 min delay during which other sample stimuli are presented

Choice phase: pick the image that is new Another yummy treat Darn, no food

Testing object-recognition memory

Medial temporal lobe (MTL)

Delayed non-match to sample results

The Mumby Box

Object recognition in rats

Comparison of lesions in monkeys and rats

Neuroanatomy of object recognition Bilateral removal of the rhinal cortex consistently results in object-recognition deficits. Bilateral removal of the rhinal cortex consistently results in object-recognition deficits. Bilateral removal of the hippocampus produces moderate deficits or none at all. Bilateral removal of the hippocampus produces moderate deficits or none at all. Bilateral removal of the amygdala has no effect on object-recognition. Bilateral removal of the amygdala has no effect on object-recognition.

Is the hippocampus involved in object recognition memory? The Case of R.B. suggests that the lesions of the CA1 region of the hippocampus (due to ischemia) can produce severe memory deficits The Case of R.B. suggests that the lesions of the CA1 region of the hippocampus (due to ischemia) can produce severe memory deficits Ischemia in animal models also produces deficits in object recognition Ischemia in animal models also produces deficits in object recognition Yet deficits in object recognition are only moderate to non-existent in other animal lesion models Yet deficits in object recognition are only moderate to non-existent in other animal lesion models Why? Why?

Mumby et al. (1996) Bilateral hippocampectomy actually blocks the damage produced by ischemia! Bilateral hippocampectomy actually blocks the damage produced by ischemia!Explanation: Ischemia causes hippocampal neurons to release glutamate, which produces damage outside of the hippocampus (particularly in rhinal cortex), although standard histological techniques do not show the damage follow-up functional imaging studies have confirmed the dysfunction. Ischemia causes hippocampal neurons to release glutamate, which produces damage outside of the hippocampus (particularly in rhinal cortex), although standard histological techniques do not show the damage follow-up functional imaging studies have confirmed the dysfunction.

The Hippocampus Rhinal cortex plays an important role in object recognition. Rhinal cortex plays an important role in object recognition. Hippocampus plays a key role in memory for spatial location. Hippocampus plays a key role in memory for spatial location. Hippocampectomy produces deficits on Morris maze and radial arm maze (Chapter 5) Hippocampectomy produces deficits on Morris maze and radial arm maze (Chapter 5) Many hippocampal cells are place cells – responding when a subject is in a particular place Many hippocampal cells are place cells – responding when a subject is in a particular place

Theories of Hippocampal Function O’Keefe & Nadel (1978) Cognitive map theory – constructs and stores allocentric maps of the world O’Keefe & Nadel (1978) Cognitive map theory – constructs and stores allocentric maps of the world Rudy & Sutherland (1992) Configural association theory – involved in retaining the behavioral significance of combinations of stimuli Rudy & Sutherland (1992) Configural association theory – involved in retaining the behavioral significance of combinations of stimuli Brown & Aggleton (1999) is involved in recognizing the spatial arrangements of objects Brown & Aggleton (1999) is involved in recognizing the spatial arrangements of objects

Synaptic Mechanisms of Learning and Memory What is happening within the brain structures involved in memory? What is happening within the brain structures involved in memory? Hebb – changes in synaptic efficiency are the basis of LTM Hebb – changes in synaptic efficiency are the basis of LTM Long-term potentiation (LTP) – synapses are effectively made stronger by repeated stimulation Long-term potentiation (LTP) – synapses are effectively made stronger by repeated stimulation

Long Term Potentiation (LTP)

Cross-section of the NMDA receptor complex