Searching for spatial localisation of memory

Brain explorers feel their way like Tom Thumb and one of methods to find a pathway is to throw pebbles, or to find a correlation between a localised brain area and a definite problem solved by this brain. One of methods for finding such correlations is based on ablation. For example, a series of experiments by Bingman and co-authors (Bingman et al., 1984; Bingman and Able, 2002) exploited the remarkable talent of pigeons to fly home rapidly from both familiar and unfamiliar release points. It turned out, first, that when released from unfamiliar site pigeons with hippocampal lesions show an initial orientation towards home that is no less accurate than that of control pigeons. The hippocampus is not, then, necessary for the efficient operation of the navigation system. Second, although hippocampal birds successfully returned to general region of their home lofts (indicating that their use of compass was intact), they did not enter their home lofts even though they were in sight. It appeared from these results that hippocampal birds were capable of homing successfully, but failed to recognise their home lofts. Subsequent studies found that if hippocampal pigeons were given sufficient postoperative experience of their home lofts (seven days or more), then they did successfully re-enter their home lofts.

These findings indicate that the hippocampus plays a critical role in memory formation. Nevertheless, despite many studies, identifying the scope and nature of memory processing by this brain structure is still remains a challenge. Results from recent studies in human and non-human subjects have suggested that the hippocampal formation and related structures are involved in certain forms of memory (episodic and spatial memory) and contribute to the transformation and stabilisation of other forms of memory stored elsewhere in the brain (Nadel and Moscovitch, 1997). More recent experiments with pigeons of different ages and different deficits and noises in sensory inputs (clock-wise, anosmic) demonstrated both the important role of the hippocampus in associability and memory storage, and a high level of plasticity in functioning of birds essential function as homing (Ioale et al., 2000; Macphail, 2002).

In general, plasticity refers to the process of making long-term changes in the brain, particularly, the changes that occur as a result of learning. It is known that during development neurones can change shape, location, function, and patterns interconnection. In the adult brain, neurones are less able to change location and function, but plasticity is still present.

Historically, there have been two opposed viewpoints about the extent to which learning and memory can be related to specific brain areas. The localizer (mosaic) theory position is that specific memories are stored in specific locations, much as mail is stored in pigeonholes in a post office (Garner, 1974; Swenson, 1991). This position was derived from the early successes of the great neuroanatomists, such as Paul Broca, in localising cortical functions. A less extreme version of this view was advanced by Pavlov. Pavlov suggested that the cortical projection areas associated with USs act as dominant foci; when excited, they radiate electrical excitation, which acts to attract the excitation produced by a CS, so that eventually the CS has the power to elicit the reflex. Thus, Pavlov saw classical conditioning as involving electrical connections between localised cortical projection areas (Schneider and Tarshis, 1975).

In contrast to this localizer theory, the gestalt theorists advocated the holistic theory which states that the brain functions as a whole through electrical field forces generated by the brain during learning. Ross Adey, Wolfgang Kö hler, and other gestalt theorists followed Karl Lashley, an American physiological psychologist, who spent over 30 years trying to determine where, if anywhere, the engram might be localised. Lashley made deep cuts between cortical regions to disrupt the kinds of connections between US-excited projection areas and CS-excited projection areas postulated by Pavlov. This produced no losses of memory or learning ability. He then systematically removed various cortical regions from thousands of rats without destroying their ability to learn and remember, thereby disproving the localizer hypothesis. The holistic theory proposed that learning leads to changes in electric fields or chemical gradients, which were postulated to surround neuronal populations and are produced by the aggregate activity of cells recruited by the learning process.

Basing on the facts that memory deficits did appear in some of his subjects and the extent of such deficits was related to the extent of the lesions-not to their location, Lashley advanced his theory of mass action as a compromise between strict localisation theories and strict holistic theories. The theory of mass action states that within functional brain regions all parts of the region are equally effective in carrying out the function normally served by the entire cortical region. This theory received clinical support. Kurt Goldstein (1939), a gestalt neuropsychologist, observed brain-damaged World War I veterans. He noted that patients with damage in the association areas adjusted by accepting that their overall intellectual abilities had been reduced. Luria, the Russian cognitive neuropsychologist has also supported the mass function (mass action) concept by developing a series of testing strategies to evaluate the amount of intact function within a damaged region (Luria and Majovski, 1977). If some intact function remains, the patient can be trained to compensate for behavioural deficits. Training is possible because of plasticity, or flexibility, in brain functioning, which decreases with age.

While Lashley found no clear evidence of localisation of memories stored in the cerebral cortex, other researchers discovered a limited type of localisation. Diamond et al. (1958) found that cats were unable to remember an auditory discrimination after removal of their auditory cortex but were able to relearn the discrimination. This suggests that learning that is specific to a particular sensory modality -such as hearing-is usually stored only in the part of the cortex specialised for processing that type of sensory input. However, other cortical areas have some potential for storing that type of information and after damage to the primary memory area for a particular modality, these secondary brain regions stores this kind of information.

One of the first series of experiments that demonstrated the role of a definite part of the brain in experiences with time belongs to Jacobsen (1936). He revealed that damage of prefrontal cortex (PFC) results in violation of delayed response behaviour. “Lobed” monkeys (i.e. the animals with surgically damage of frontal lobe) coped with simple discrimination task but they could not solve a problem when requested to choose a cup under which a piece of food disappeared before their eyes. It was, as it were, following to the rule “out of sight – out of mind”. In early experiments with PFC-ablated chimpanzees the animals which were trained to use sticks for getting food, after surgical operation were able to perform this action only if they kept eyes both on the stick and the food simultaneously.

Later, when dealing with individual neurones became possible as well as mapping brain activity using magnetic resonance imaging, the behavioural method of delayed reaction has became a basis for studying functioning of the frontal lobe from single cells to how cells communicate with each other to how animals behave. For example, research of Goldman-Rakic (1995) on non-human and human primates included functional metabolic mapping, single cell recording in behaving primates, and lesions and drug manipulations of behaviour in monkeys.

Experiments on monkeys cleared that a major contribution of the PF cortex to cognition is the active maintenance of behaviourally relevant information “online”. Experiments in many laboratories have verified that damage to the PF cortex in humans and monkeys tends to produce impairments when available sensory information does not clearly dictate what response is required. For example, PF lesions impair the ability to solve spatial delayed response tasks in which a cue is briefly flashed at one of two or more possible locations and the monkey must direct an eye movement to its remembered location. However, no impairment is observed if there is no delay and monkeys can immediately orient to the cue. Thus the PF cortex seems critical when the correct action must be selected using recent memory and knowledge of task demands (Funahashi et al., 1993; Rainer et al., 1998).

The correlation has been revealed between accuracy in performance of delayed response procedure and age-specific development of frontal lobe at least in primates. It turned out that in rhesus monkeys the ability to cope with such tests become apparent at the age of 2-4 months while in human infants after 8 months. The infants under 8 months, in which functional organisation very much differs from adults, are as bad in coping with the delayed response tests as monkeys with the surgically damaged lobe. In these cases behaviour is governed by current conditioning, not by mental representation. Both babies and PFC-ablated monkeys repeat again and again just the response that was reinforced before instead of changing their reaction in accordance with the new information obtained. Even if the infants see a toy being moved into the left box from the right box, they insist on choosing the left one where the desired thing has been before (Goldman-Rakic, 1992).

It is worth noting that normal ageing, at least in mammals, is frequently accompanied by a decline in the cognitive capacities supported by the prefrontal cortex. For example, aged rats and monkeys display deficits on multiple testing procedures known to require the functional integrity of the frontal cortex. It was shown that ageing is not accompanied by significant neuronal loss. Instead, intricate biochemical mechanisms affect age-related decline in the information processing capacities (O’Donnell et al., 1999).

The nonhuman primate brain has been used as an animal model of human brain development and brain function. Comparative analysis of development revealed the close parallel between the developmental time course of memory processes in infant monkeys and human infants. In human children procedural memory emerges very early after birth, while associative memory emerges later, around the age of four or five. Similar dissociation of memory processes also is found in monkeys. On tasks measuring procedural memory, monkeys as young as three months of age could perform as efficiently as adults, while associative memory develops later (see Bachevalier and Mishkin, 1989).

Results obtained in Goldman-Rakic laboratory (see: Goldman-Rakic, 1992, 1995) showed that, among very dramatic aberrations observed in a schizophrenic brain, in which frontal lobe dysfunction is prominent, one of the main differences lies in the organisation of working memory. When performing delayed response tests, people suffering from schizophrenia usually repeat the answer they gave before although it had been already clear that this answer was wrong. Schizophrenic mind misapprehends events of external world as a series of disconnected occurrences. Their behaviour in this context is governed not by a balance between current external information and mental representations but by on-line reaction to external stimuli.

Although cause of schizophrenia remains a mystery, evidence suggests that it is at least 80% heritable, stemming from complex interactions among several genes and non-genetic influences. Patients show abnormal activation of the prefrontal cortex, which is required for such " executive" functions associated with the prefrontal cortex and working memory, such as initiation and overall control of deliberate actions, goal directed behaviour, attention, planning, and decision making.

Schizophrenia is a disease unique to humans. It is not that prefrontal cortex is the part of the brain that really helps to separate man from beast, but in animals’ ability to solve problems that require active working of the prefrontal cortex is limited by species-specific level of cognition and guided by selective attention for stimuli and specific philtres for perception. We will see in Part VII that cognitive skills may vary within wide range among individuals belonging to the same species. Nevertheless, it is of no doubt that humans are championed in cognitive abilities as well as in mental diseases. At the same time cellular and molecular mechanisms of memory are common for many species and this gives a great opportunity to discover universal laws of memory on animal models.