Rorden, C., and Karnath, H. (2004). Using human brain lesions to infer function: a relic from a past era in the fMRI age? Nature Reviews Neuroscience, 5, 812-819.
Lecture Outline:
Introduction to patient studies and the lesion method.
Types of brain damage, example, terminology
Single and double dissociation (example)
Limits to the lesion method
What’s a control group?
Patient Studies:
A major source of knowledge about brain and mind.
Causes:
Trauma
Stroke / Vascular accidents
Tumor
Degenerative and Infectious Disease
Epilepsy, Neuropsychiatric Disorders
Neurosurgery
Neuropsychological Deficits:
Agnosia: Loss of ability to recognize objects, people, sounds, shapes, or smells; the inability to attach appropriate meaning to objective sense-data (“The man who mistook his wife for a hat”).
Aphasia: A general term relating to a loss of language ability.
Apraxia: A general term for disorders of action.
Amnesia: Lack of mnemonic abilities.
Ataxia: Poor coordination and unsteadiness due to failure to regulate the body's posture, strength, and direction of limb movements.
Many Subtypes:
Visual agnosia is associated with lesions of the left occipital and temporal lobes.
Form agnosia: Patients perceive only parts of details, not the whole object.
Finger agnosia: The inability to distinguish the fingers on the hand, present following lesions of the parietal lobe.
Simultanagnosia: Patients can recognize objects or details in their visual field, but only one at a time.
Associative agnosia: Patients can describe visual scenes and classes of objects but still fail to recognize them. For example, knowing a fork is something you eat with but mistaking it for a spoon.
Apperceptive agnosia: Patients are unable to distinguish visual shapes and so have trouble recognizing, copying, or discriminating between different visual stimuli.
Prosopagnosia: Also known as faceblindness or facial agnosia.
Behavioural Testing:
The existence of selective deficits can tell us something about the way function is organised in the brain.
The goals are to relate brain anatomy to behaviour and to investigate mental processes.
Requires behavioural tasks.
Tasks should tell us about the patient’s deficits:
What functions are compromised?
What functions are spared?
Dissociating Cognitive Functions and Brain Regions:
Cognitive functions can be dissociated (separated to a degree) from each other through selective impairment.
The same is true for the function of brain regions.
Dissociation studies require a minimum of two groups and two tasks.
Comparison between patient/control groups shows deficit.
Two tasks are needed to determine whether a deficit is specific to a particular function or reflects a more general impairment.
Single Dissociation:
Demonstrates that a patient group performs poorly on one task (e.g., declarative memory) compared to a control group, while performance on another task (e.g., nondeclarative memory) is relatively spared.
Suggests the involvement of a specific brain region (e.g., temporal lobes) in the impaired function.
However, it does not definitively prove that the brain region is not involved in the spared function.
Limitations of Single Dissociation:
The conclusion that the temporal lobes are involved in declarative memory, and NOT in nondeclarative memory, does NOT follow.
Poor performance of patients might be caused by another factor, such as a deficit in concentration. The test of declarative memory might require more concentration than the test of nondeclarative memory.
Double Dissociation:
Provides strong evidence that there are cognitive processes critical for task X that are not critical for task Y, and vice versa, and that brain-area A is critical for task X but not for task Y etc.
Double dissociations provide evidence that the observed differences in performance reflect functional differences between the groups, rather than unequal sensitivity of the two tasks.
Participants don‘t have to be perfectly intact on either task, they just need to be significantly better at one task than the other.
Double Dissociations:
Involves two patient groups, each with damage to a different brain area, and two tasks.
Patient group 1 (e.g., temporal lobe lesion) is impaired on task X but not task Y.
Patient group 2 (e.g., cerebellum lesion) is impaired on task Y but not task X.
This reciprocal pattern of impairment provides strong evidence for the functional independence of the two cognitive processes and the selective involvement of the two brain areas.
Limitations of Patient Studies:
Assumption of modularity
Lesions extensive and varied
Lesion anatomy inaccurate, connections not considered
Individual differences in functional anatomy
Poor temporal resolution
Modularity of Function:
Assumption that mental processes occur with a high degree of isolation from other mental processes, and when one area is damaged, other regions do not adapt their function.
Brain plasticity: In reality, the brain reorganizes quickly. Intact regions change their behaviour so it is difficult to infer function of damaged region
Processes/dynamics neglected: It is neurons, not black boxes, that perform the function - but how?
Lesions Extensive and Varied:
Most work is done with patients who have large lesions.
Lesions often damage several functional centres, so there are few patients with ‘pure’ deficits.
Lesion size and location are variable, making it hard to find a group of similar patients. Inferences from single patients are weak.
Individual differences in recuperative history.
Lesion Anatomy Inaccurate and Connections Not Considered:
Anatomical scans show regions that are destroyed, but intact regions may not be functioning.
Regions may be disconnected from other regions that provide input.
Individual Differences in Functional Anatomy:
We assume that an anatomical region of the brain does the same function in all individuals.
Clearly violated assumption – e.g. Wada test indicates the left hemisphere predominates in language processing in most, but not all, individuals.
Variability of function across individuals reduces the power of group studies.
Poor Temporal Resolution and Experimental Control:
Even if patient studies establish which regions are necessary for a task, and its inferred cognitive processes, it is not possible to infer the stages of processing.
A memory deficit may arise from a failure of encoding, retention, or recall.
There is no experimental control over lesion location, but animal studies using experimental ablation can provide this.
Other methods overcome these limitations.
Benefits of Patient Studies:
Show which areas are necessary for a particular cognitive function (double dissociation).
Show cognitive, emotional, social consequences of a deficit (example: Damasio‘s patient Elliot).
Cost- and time-effective, single-case studies are possible (e.g. H.M., no experimental design necessary, exploratory observations possible).
Can be done right (overlay plots and control groups) to limit criticism.
Why We Cannot Localize Speech Production in This Area:
Damage is not limited by functional boundaries.
The lesion might be smaller than the functional module.
Interindividual differences in brain organization.
The result might reflect the increased vulnerability of the region to injury (e.g., because of vasculature).
The area might just be interconnected with the actually relevant area (indirect disruption).
Importance of Control Group:
We need to include a CONTROL GROUP of PATIENTS with right-hemisphere brain damage but without VFDs (visual field deficits).
In this way, we CONTROL for the effect of right-hemisphere damage and contrast only across the factor of VFD presence.
VFDs are associated most strongly with damage to the occipital cortex (optic radiations and visual areas).
Summary:
Patient/lesion methods can reveal novel insights about brain function without any experimental design.
Done properly (with double dissociation groups of patients and an appropriate control group), some of the drawbacks can be prevented.