medially) is the most elaborated of all the PFC subcomponents in humans compared to extant apes, occupying the largest area at 28 000 mm3 with ~500 million neurons. Despite the neuron number, the neuronal density is relatively decreased. Furthermore, dendritic spines and density counts are higher compared to other PFC areas. Importantly, for developing humans, the FPC develops relatively late in life, often in the fourth decade as maturation of dendritic spines is protracted [12–14]. Metacognition or self reflection is considered to be an important component of the FPC region. Other higher cortical func
tion attributes of the FPC include episodic memory, multitasking, relational integration, self referential evaluation, and introspection [15,16]. The net result of the sophisticated PFC subcomponent evolution was key for evolving hominoids, allowing fewer errors through imitation of others, engaging in mental time travel, and imaging actions before actual engagement of actions. Archeological evidence from several skulls, including the Bodo skull from Ethiopia (~600 kya), the Kabwe skull from Zambia (~300 kya), and Saldahna man from South Africa, shows that, although having large brow ridges, the slope of the inner frontal brain case is not significantly different from that of modern humans [17]. This implies that their frontal lobes had reached modern Homo sapiens size and shape by ~600–300 kya. This may be considered relatively early in the history of our evolution and long before the cultural evolution dated to 70–50 kya [18].
Ventral and Dorsal Premotor Cortices
Among earlier primates, the ventral premotor cortex (VPMC) connected to corticospinal projections to the seventh nerve facial nucleus and upper cervical spinal cord segments.
These projections subserved facial motility; facial expression refined motor control of the mouth, head, and arm reaching movements. The dorsal premotor cortex (DPMC) pre supplementary motor area (pre SMA) incorporated leg control [19]. Taken together these provided us with phenotype variations today including:
• working memory
• initiation
• disinhibition
• attention
• monitoring
• emotional control
Working Memory
Working memory is also referred to as short term memory, measured in seconds to minutes and allowing mental processing of information such as occurs with manipulat
ing numbers, constructing a sentence, or just mere thoughts. This differs from episodic memory, which is measured in minutes (episodic short term) to many years (episodic long term). Hence working memory has been likened to the brain’s operating system that is integral to the core frontal lobe functions of attention, disinhibition, and initi
ation. The expansive working memory circuitry comprises a frontal, temporal, parietal, and subcortical network. A fundamental assignment of the PFC is working memory or the physiological process of monitoring information or items while engaging in further
computation as the information is being held “online” [20,21]. The evolution of these abilities is relatively specific to primates; non primate mammals seem either to lack this ability or have more rudimentary abilities in this regard.
Such statements, though, are prone to modification as rodents are able to learn the radial maze task, which suggests they have the ability to remember and monitor infor
mation at the same time. Several investigators in addition to Baddeley have come up with terms for these PFC processes. In addition to Baddeley’s working memory [22], Dehaene’s global workspace and Duncan’s multiple demand theories have been proposed [23]. These theories all define roles for both the PFC and posterior parietal cortex and that both cortical regions contribute to working memory.
Intraneuronal recordings have implicated the DLPFC (BA 46 and 9) activity during the delay period in support of the cellular basis of sustaining information for ultimate action planning. The monitoring component (such as tracking an important stimulus) of this process has been attributed to the mid DLPFC and the posterior parietal regions. The posterior parietal area is involved with the further manipulation of the information being held online, also referred to as the epoptic process by Petrides [20]. The mainten anceof
information component of working memory circuitry is within the superior temporal gyrus for auditory information and the inferotemporal cortex for faces and items. The posterior parietal region, for example, contains circuitry permitting the processing of information required for arithmetic functions and mental rotation of objects (PFC BA 46 axons connecting to layers 1–3 of the intraparietal sulcus). The mid DLPFC is required for monitoring information, during which time further processing or manipulation of such information is being done [24,25] (see Figure 3.7). The retrieval of memories is accomplished by the mid ventrolateral PFC (VLPFC) and differs from maintenance of information of working memory [21,26].
The process of working memory evolution has been envisaged by Read and Diamond as on a scale of 1–7, with chimpanzees having acquired level 2 compared to modern humans at a level 7 working memory capacity [27,28] (see Figure 3.6). These studies of chimpanzee short term memory capacity assigned a level 2, possibly 3, that was based on nut cracking, gestures, and object manipulation studies. Chimpanzees are able to coordin
ate manipulation of two objects or items (rarely three) by three years of age. Examples include Congo basic chimpanzees termite foraging with “fishing sticks.” Human infant short term working memory capacity growth trajectories differed markedly in compari
son to those of chimpanzees in the 7–144 months age period. These studies corroborate archeological data of working memory capacity with the common ancestor of hominins (working memory level 7) and Pan (working memory level 2–3) [27].
Working Memory as a “Missing Link”
Working memory may be considered a “missing link” in early modern humans, sparking the cultural evolution of creativity, language, and visual art development. The elaboration of working memory evolution based on the extensive frontoparietal circuitry, and subse
quently the advent of what has been termed by Wynne and Coolidge as enhanced working memory (EWM), may be regarded as a major cognitive watershed in human evolution.
EWM evolved around 200 and 40 kya and will be elaborated on further in Chapter 6 [29].
Neuroplasticity capabilities and evolution of the tertiary association cortices would serve as the basis of more sophisticated human abilities such as advanced tool making, visual art forms, and language, which included the component of recursion [30].
Ventral and Dorsal Premotor Cortices 91
Working memory functions and manifestations of disorders are recognized in regard to multitasking, planning for the future, engaging in abstract thoughts, and retaining ver
bal and nonverbal information for further processing. Some of these are often referred to as executive functions, including sustained attention to allow the temporal organization of behavior. These may be summarized to involve task setting, task initiation, monitor
ing of the motor activity, the detection of possible errors, and the facilitation of self
regulation [31]. The neural circuitry that underlies these functions includes the frontal subcortical circuits: the left DLPFC (task setting), right DLPFC (monitoring and error detection), bilateral superior medial frontal circuits (initiation of the task), and medial orbital frontal cortex (OFC) (regulation of behavior) [32].
Initiation
The intention to act is perhaps easier to understand when deficient. Various terms such as abulia, lack of conation (Latin: conatus – natural tendency to strive toward or have directed effort), or cerebral torpor have been used. In clinical neurology, the spectrum of behaviors ranges from akinetic mutism to abulia, with lesser forms termed hypobulia, apathy, and alexithymia. These denote the various degrees from no movement to some movement. Alexithymia refers to an inability to identify and describe one’s own emo
tions. Such syndromes may form part of any neurological disorder, most commonly after stroke and recognized with schizophrenia. In the latter, the avolitional component is a core feature, and anhedonia, asociality, and alogia are part of the clinical manifestations of the primary avolitional deficit [33]. Additionally, the loss of creativity, emotion, initia
tive, and curiosity may be manifest [34].
Abulia may underlie a number of behavioral disorders, including episodic dys
memory, which is in turn ascribed to inattention as well as impaired registration and poor retrieval, and self neglect. In its severest form it can present as senile squalor syn
drome. In addition, lack of empathy and emotional flatness represent distressing behav
iors for family and friends, and ritualistic and stereotyped behavior may take the form of various repetitive activities such as feasting on the same foods, humming, foot tap
ping, grunting, clock watching, and punding (extended stereotyped, purposeless behav
iors). The cause of abulia is important and may present with coma and akinetic mutism that are usually viewed as portending a grave prognosis. Indeed, that was the case with two examples, both young women with similar tegmentothalamic lesions, one with deep venous system thrombosis post partum and the other secondary to viral encephal
itis or Mycoplasma pneumonia. Both recovered well to complete functionality (Figure 5.1).
Viral encephalitis causing transient coma, and tegmentothalamic lesions with good recovery, have also been reported several times by other investigators as due to different organisms [35].
Disinhibition
Disinhibition may manifest with impulsivity, socially inappropriate behavior, and abnor
mal eating behaviors, and affect the extensive mirror neuron network disruption, causing a wide array of field dependent behaviors. The latter may be more elementary, such as imitation behavior, or more complex forms (discussed under the section on mirror neur on circuit disruption) [36].
Attention
Attention is a fundamental brain function that is mediated by cerebral networks for alertness and arousal. Attention differs from working memory in that it allows a specific stimulus, whether sensory or cognitive in nature, to be given priority or preference over and above other competing stimuli. Working memory enables the maintenance of certain limited information for a few seconds to minutes, at most, for the further processing or manipulation of that retained information. Attention is commonly considered as one of the following:
• sustained attention: maintenance of consistent behavior in the context of repetitive or continuous activity;
• focused attention: responding to specific auditory, tactile, or visual stimuli;
• selective attention: maintenance of the behavioral response in the face of competing or distracting stimuli;
• divided attention: being able to respond concurrently to several tasks;
• alternating attention: the ability to vary the focus of attention and navigate between tasks, also termed mental flexibility [32,37].
Monitoring
Monitoring of intended actions is largely within the frontopolar cortex domain and will be discussed in more depth under the relevant section. Clinical syndromes seen when
“monitoring” is impaired include perseveration and impersistence. Perseveration refers
Figure 5.1 Athymhormia spectrum disorders: akinetic mutism, abulia, hypobulia, apathy. Two different processes causing coma and akinetic mutism in young women due to bilateral tegmentothalamic lesions.
Akinetic mutism secondary to deep venous system thrombosis postpartum (arrows). Right image due to encephalitis presumed Mycoplasma pneumonia related (arrows). Both recovered to good functionality.