**Abstract**

Beyond its established role in declarative memory function, the hippocampus has been implicated in varied roles in sensory processing and cognition, particularly those requiring temporal or spatial context. Disentangling its known role in memory from other cognitive functions can be challenging, as memory is directly or indirectly involved in most conscious activities, including tasks that underlie most experimental investigations. Recent work from this lab has examined the directional influence from the hippocampus on cortical areas involved in task performance, including tasks requiring movements, sensory processing, or language judgments. The hippocampus shows preferential connectivity with relevant cortical areas, typically the region critically involved in task performance, raising the possibility that the hippocampus plays a role in cognitive control. Minimal criteria for a role in cognitive control are proposed, and hippocampal connectivity with sensorimotor cortex during a non-mnemonic motor task is shown to meet this standard. Future directions for exploration are discussed.

**Keywords:** hippocampus, cortex, connectivity, PPI, cognitive control, sensorimotor, language

### **1. Introduction**

Since its earliest description in 1587, many different functions have been ascribed to the hippocampus, each based on the available techniques and prevailing understanding of brain function. The earliest hypotheses were based on its observed anatomical connections. The hippocampus was first believed to be olfactory, based on erroneous observations suggesting direct olfactory input [1]. Olfactory input to the hippocampus is in fact indirect; except for a role in odorous memories, olfaction is no longer believed to be the hippocampus' primary function.

By the early twentieth century, a role of the brain in emotional and cognitive states had been well-established, and procedures were developed to better trace brain pathways and identify brain lesions. The hippocampus was identified as one structure within the "limbic lobe". Including the entire hippocampal formation, cingulate gyrus, and associated areas, Papez theorized this region to be involved in the expression of emotional behaviors [2, 3]. Support for this idea was seen in the

experiments of Klüver and Bucy, who reported that resection of the medial temporal lobe (including the hippocampal formation and nearby amygdaloid complex) had extreme effects on emotional behaviors [4–6].

In the 1950s, the spontaneous activity of the hippocampus was noted to bear a consistent relationship to various states of consciousness [7], generating several hypotheses about high-level cognitive functions. These ideas were largely dismissed, as researchers had demonstrated that lower mammals could still function (albeit with deficits) after the hippocampus was experimentally removed [8]. Anatomical studies further refined our knowledge of hippocampal connections across the brain. After several stages of processing, information from every sensory modality funnel into the hippocampus via the entorhinal cortex, with multiple senses sometimes combined; the hippocampus indirectly projects to the entire cerebral cortex, mostly via the subiculum [9].

When Scoville and Milner surgically resected a patient's hippocampus in an attempt to relieve epileptic seizures, the patient was unable to form new episodic and declarative memories (i.e., those that can be verbalized) [10]. This finding firmly established a role for the hippocampus in these types of learning and memory, eventually replacing the prevailing inhibition theory of the hippocampus. The inhibition theory had been based on observations of hyperactivity and difficulty learning to inhibit responses following hippocampal damage [11, 12].

An additional theory of hippocampal function was developed in 1971 with O'Keefe's discovery of hippocampal place cells in rats [13]. The intensity of these cells' activity depended on the animal's location within a baited maze. Extensive study was undertaken to identify which environmental cues were used by the animal to recognize its spatial position, and whether activity of the place cells showed spatially selectivity when the animals were placed in a different environment [14, 15]. Navigational problems were observed following hippocampal lesions [16, 17]. Whether the mnemonic and spatial properties are functionally distinct or different facets of the same overarching function was a matter of debate, however, which continues to this day [18–21].

Through most of the twentieth century, theories of hippocampal function relied on evidence from lesion and anatomical studies, plus recordings of electrical activity. The advent of neuroimaging methodologies, particularly functional magnetic resonance imaging (fMRI), allowed hippocampal function to be studied noninvasively in humans. This technique detects regional changes in oxygenated blood resulting from increased neuronal activity, providing the means to identify brain areas based on their functional activity. With the advent of fMRI, investigators could verify in humans the patterns of functional activity observed in non-human animals, adding more complex tasks to further elucidate functional properties.

Early neuroimaging studies examined mean changes in neural activity that differentiated between blocks of time where different tasks were performed, tasks that differed in their cognitive requirements (e.g., memory). Soon, methods were enhanced to identify neural activity during individual trials [22]. Consistent with its theorized mnemonic function, regional increases in hippocampal activity were observed during learning and recall; furthermore, greater activity was observed during those learning trials where a stimulus was presented that was later recalled successfully [23, 24]. Similarly, hippocampal activity during virtual navigation experiments could be correlated with spatial cues [25–27], consistent with its proposed function as a cognitive map. Thus, the two prevalent theories of hippocampal function were both supported. Additional studies described new properties, such as sensitivity to the temporal duration or spatial relationships [28–30], and a role in scene perception and reconstruction [31]. Some interpret these properties as contextual elements required for memory recall [19, 28, 32]; others suggest a more

### *Hippocampal Influences on Movements, Sensory, and Language Processing: A Role in Cognitive… DOI: http://dx.doi.org/10.5772/intechopen.100122*

fundamental perceptual role in identifying changes in the environment, which may consequently be incorporated into memories [33, 34]. Differences between these viewpoints are often nuanced. As more information about hippocampal activity has accrued, other roles for the hippocampus have also been suggested, including a role in conscious perception [35–37] and cognitive control [38–40].

The traditional "activation" analysis of fMRI data is patterned on traditional methods for analyzing electrical activity from localized regions of the brain. It assumes all information in a neuron's electrical activity is carried through its frequency of discharge, yet additional information is carried in the hippocampal temporal pattern of activity [41–43]. Cognitive functions also require interactions between neural structures. With the development of connectivity analysis from fMRI data early this century, influences between brain regions could be inferred based on the temporal pattern of neural activity. Early connectivity studies used *functional connectivity*, any of several statistical methods that examines correlations in neural activity between brain regions. Although useful for broadly identifying connections and identifying their abnormalities, the direction of influence in these studies cannot be known with certainty; two regions with correlated activity, for example, might both be influenced from a third region. Methods were soon developed to analyze *effective connectivity*, the influence of one brain region over another.

This chapter will focus on the influence of the hippocampus across a variety of cognitive domains; as such, effective connectivity studies will be emphasized, with particular attention to those that use *psychophysiological interactions* (*PPI*). This form of effective connectivity analysis reveals task-specific influences between regions. Results show a pattern whereby the hippocampus consistently influences activity in cortical areas involved in task performance, including tasks requiring movements, sensory processing, language judgments, and memory. Careful consideration of results and the cognitive requirements of these tasks suggests hippocampal connectivity could play a role in cognitive control, perhaps in parallel with the role of prefrontal cortex in translating thoughts into action.
