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NE33CH09-SalzmanARIANNUALREVIEWS14 May 17:24FurtherAnnu. Rev. Neurosci..33:173-202. Here we review studies using anatomical, lesion, and neurophysiological approaches to investigate the representation and utilizationof cognitive and emotional parameters. We propose that these mentalstate parameters are inextricably linked and represented in dynamic neural networks composed of interconnected prefrontal and limbic brainstructures. Future theoretical and experimental work is required to understand how these mental state representations form and how shiftsbetween mental states occur, a critical feature of adaptive cognitive andemotional behavior.173

NE33CH09-SalzmanARI14 May 17:24ContentsAnnu. Rev. Neurosci..33:173-202. For personal use only.INTRODUCTION . . . . . . . . . . . . . . . . . .MENTAL STATES:SYNTHESIZING COGNITIONAND EMOTION . . . . . . . . . . . . . . . . .AN ANATOMICAL SUBSTRATEFOR INTERACTIONSBETWEEN EMOTION ANDCOGNITION . . . . . . . . . . . . . . . . . . . .Amygdala . . . . . . . . . . . . . . . . . . . . . . . . . .Prefrontal Cortex . . . . . . . . . . . . . . . . . .Anatomical Interactions Betweenthe PFC and Amygdala . . . . . . . . . .THE ROLE OF THE AMYGDALAAND THE PFC INREPRESENTING MENTALSTATES: LESION STUDIES . . . . .Amygdala . . . . . . . . . . . . . . . . . . . . . . . . . .Prefrontal Cortex . . . . . . . . . . . . . . . . . .Prefrontal-Amygdala Interactions . . .NEUROPHYSIOLOGICALCOMPONENTS OFMENTAL STATES . . . . . . . . . . . . . . .Neural Representations ofEmotional Valence and Arousalin the Amygdala and the OFC . . .Neural Representations of CognitiveProcesses in the PFC . . . . . . . . . . . .NEURAL NETWORKS ANDMENTAL STATES: ACONCEPTUAL ANDTHEORETICAL FRAMEWORKFOR UNDERSTANDINGINTERACTIONS BETWEENCOGNITION AND EMOTION . .CONCLUSIONS . . . . . . . . . . . . . . . . . . . ODUCTIONThe past century has witnessed a debate concerning the nature of emotion. When the brainis confronted with a stimulus that evokes emotion, does it first respond by activating a rangeof visceral and behavioral responses, which areonly then followed by the conscious experiencePFC: prefrontalcortex174Salzman·Fusiof emotion? For example, when we encountera threatening snake, does autonomic reactivity,as well as behaviors such as freezing or fleeing, emerge prior to the feeling of fear? Thisview, championed by the psychologists WilliamJames and Carle Lange around the turn of thetwentieth century ( James 1884, 1894; Lange1922), has attracted renewed interest because ofthe influential work of Damasio and colleagues(Damasio 1994). Alternatively, do visceral andbehavioral responses occur as a result of centralprocessing in the brain—processing that givesrise to emotional feelings—which then regulates or controls a variety of bodily responses[a possibility raised decades ago by WalterCannon (1927) and Philip Bard (1928)]?Neuroscientists have often sidestepped thisdebate by operationally defining a particularaspect of emotion—e.g., learning about fear—and using a specific behavioral or physiologicalassay—e.g., freezing—to investigate the neural basis of the process (Salzman et al.).This approach is agnostic about which responsecomes first: the visceral and behavioral expression of emotion or the feeling of emotion. Butit has proven powerful in helping to identifyand characterize the neural circuitry responsible for specific aspects of emotional expression and regulation. These investigations haveshown that one brain area, the amygdala, playsa vital role in many emotional processes (Baxter& Murray, Lang & Davis, LeDoux, Phelps & LeDoux) and that theamygdala and its interconnections with the prefrontal cortex (PFC) likely underlie many aspects of the interactions between emotion andcognition (Barbas & Zikopoulos, Murray& Izquierdo, Pessoa, Price).Today, we still lack a resolution to the original debate concerning the relationship betweenemotional feelings and the bodily expression ofemotions, in large part because both viewpointsappear to be supported in some circumstances.Emotional feelings do not necessarily involvevisceral and behavioral components andvice versa (Lang 1994). But neurobiologicaladvances—in particular, emerging data on theintimate relationship between the PFC and

Annu. Rev. Neurosci..33:173-202. For personal use only.NE33CH09-SalzmanARI14 May 17:24limbic areas such as the amygdala—beginto suggest a solution. As discussed below,the amygdala is essential for many of thevisceral and behavioral expressions of emotion;meanwhile, the PFC—especially its medialand orbital regions—appears to be responsiblefor many of the cognitive aspects of emotionalresponses. However, recent studies suggestthat both the functional and the electrophysiological characteristics of the amygdala andthe PFC overlap and intimately depend oneach other. Thus, the neural circuits mediatingcognitive, emotional, physiological, and behavioral responses may not truly be separableand instead are inextricably linked. Moreover,we lack a unifying conceptual frameworkfor understanding how the brain links theseprocesses and how these processes change inunison.MENTAL STATES:SYNTHESIZING COGNITIONAND EMOTIONHere, we propose a theoretical foundation forunderstanding emotion in the context of itsintimate relation to the cognitive, physiological, and behavioral responses that constituteemotional expression. We review recent neurobiological data concerning the amygdala andthe PFC and discuss how these data fit into aproposed framework for understanding interactions between emotion and cognition.The concept of a mental state plays acentral role in our theoretical framework.We define a mental state as a disposition toaction—i.e., every aspect of an organism’s inner state that could contribute to its behavioror other responses—which may comprise allthe thoughts, feelings, beliefs, intentions, active memories, and perceptions, etc., that arepresent at a given moment. Thus mental statescan be described by a large number of variables,and the set of all mental state variables couldprovide a quantitative description of one’s disposition to behavior. Of note, the identification of mental state variables is constrained bythe language we use to describe them. Conse-quently, mental state variables are not necessarily unique, and they are not necessarily independent from each other. Mental state variablesneed not be conscious or unconscious becauseboth types of variables can predispose one toaction. Overall, an organism’s mental state incorporates internal variables, such as hunger orfear, as well as the representation of a set of environmental stimuli present at a given moment,and the temporal context of stimuli and events.Any given mental state predisposes an organismto respond in certain ways; these actions may becognitive (e.g., making a decision), behavioral(e.g., freezing or fleeing), or physiological (e.g.,increasing heart rate). Mental state variables areuseful theoretical constructs because they provide quantitative metrics for analyzing and understanding behavioral and brain processes.The concept of a mental state is intimatelyrelated to, but distinct from, what we call a brainstate. Each mental state corresponds to one ormore states of the dynamic variables—firingrates, synaptic weights, etc.—that describe theneural circuits of the brain; the full set of values of these variables constitutes a brain state.How are the variables characterizing a mentalstate represented at the neural circuit level—i.e., the current brain state? This is one way tophrase a fundamental and long-standing question for neuroscientists. At one end of the spectrum is the possibility that each neuron encodesonly one variable. For example, a neuron mayrespond only to the pleasantness of a sensorystimulus, and not to its identity, to its meaning, or to the context in which the stimulus appears. When neurons encode only one variable,other neurons may easily read out the information represented, and the representation can, inprinciple, be modified without affecting othermental state variables.One of the disadvantages of the type of representation described immediately above is wellillustrated by what is known as the “bindingproblem” (Malsburg 1999). If each neuron represents only one mental state variable, then itis difficult to construct representations of complex situations. For example, consider a scenewith two visual stimuli, one associated with Amygdala, PFC, and Mental States175

ARI14 May 17:24reward and the other with punishment. Thebrain state should contain the information thatpleasantness is associated with the first stimulus and not with the other. If neurons represent only one mental state variable at a time,like stimulus identity, or stimulus valence, then“binding” the information about different variables becomes a substantial challenge. In thiscase, there must be an additional mechanismthat links the activation of the neuron representing pleasantness to the activation of theneuron representing the first stimulus. Onesimple and efficient way to solve this problem isto introduce neurons with mixed selectivity toconjunctions of events, such as a neuron that responds only when the first stimulus is pleasant.In this scheme, the representations of pleasantness and stimulus identity would be entangledand more difficult to decode, but the numberof situations that could be represented wouldbe significantly larger. As discussed below, different brain areas may contain representationswith different degrees of entanglement.How do emotions fit into the conceptualframework of mental states arising from brainstates? One influential schema for characterizing emotion posits that emotions can varyalong two axes: valence (pleasant versus unpleasant or positive versus negative) and intensity (or arousal) (Lang et al. 1990, Russell1980). These two variables can simply be conceived as components of the current mentalstate. Two mental states correspond to different emotions when at least one of the two mental state variables—valence or intensity—is significantly different. Thus, variables describingemotions have the same ontological status asdo variables that describe cognitive processessuch as memory, attention, decision-making,language, and rule-based problem-solving. Below, we describe neurophysiological data documenting that variables such as valence andarousal are strongly encoded in the amygdala–prefrontal circuit, along with variables relatedto other cognitive processes. We suggest thatneural representations in the amygdala maybe more biased toward encoding mental statevariables characterizing emotions (valence andAnnu. Rev. Neurosci..33:173-202. For personal use only.NE33CH09-Salzman176Salzman·Fusiintensity). PFC neurons may encode a broaderrange of variables in an entangled fashion, reflecting the complexity of the behavior and cognition that are its putative outputs.The concept of a mental state unites cognition and emotion as part of a common framework. How does this framework contribute tothe debate about the relationship between emotions and bodily responses? We argue that theissues raised in the debate essentially dissolvewhen one conceptualizes emotions as part ofmental states: Neither emotional feelings norbodily responses necessarily come first or second. Rather, both of these aspects of emotion are outputs of the neural networks thatrepresent mental states. Furthermore, all thethoughts, physiological responses, and behaviors that constitute emotion are part of an ongoing feedback loop that alters the dynamic,ever-fluctuating brain state and generates newmental states from moment to moment.How do mental states that integrate emotion and cognition arise from the activityof neural circuits? Below, we describe a potential anatomical substrate—the amygdala–prefrontal circuit—for emotional-cognitive interactions in the brain and how neurons inthese areas could