Delusional misidentifications and duplications

Delusions are pathologic beliefs that remain fixed despite clear evidence that they are incorrect. They are not conventional beliefs of a culture or religion. Often bizarre in content and held with absolute certainty, delusions can cause significant morbidity. Their pathogenesis in primary psychotic disorders and neurologic disorders remains unknown, with theories encompassing psychological, cognitive, neurochemical, and structural anomalies. This article reviews the cognitive and anatomic systems underlying two delusional misidentification syndromes, reduplicative paramnesia and Capgras syndromes, and related disorders of confabulation and anosognosia.

The division between delusions in psychiatric (primary) and neurologic-systemic disorders (secondary) is artificial since psychiatric disorders with delusions (e.g., schizophrenia) have functional and structural brain pathology. Like psychiatric delusions, neurologic misidentification disorders may be associated with paranoia and are usually personally significant. Schizophrenic delusions usually involve 1) influence (e.g., thought control, broadcasting or insertion), 2) persecution or paranoia, and 3) self-significance (e.g., grandeur, reference, religious, guilt). Schizophrenic delusions are not consistently associated with lateralized or localized brain metabolic abnormalities.¹ Delusional disorder is a psychotic syndrome with prominent non-bizarre delusions (e.g., my wife is having an affair) lasting for at least 1 month, including erotomania, grandiose, jealous, persecutory, somatic, and mixed. Simple delusions are unstructured, variable, and often paranoid. Complex delusions usually focus on specific content, with an elaborate web of explanations in patients with relatively preserved intellect, as intellect is recruited in the service of the delusion.²

Improved diagnostic techniques have increased identification of neurologic disorders among patients with delusions. For example, Capgras syndrome was a psychiatric disorder 50 years ago, but neurologic disorders are now recognized in most cases.³ A wide spectrum of systemic and neurologic disorders cause simple and complex delusions.⁴ Content-specific delusions predominate in neurologic patients^3,5,6 (table 1), usually misidentification and reduplication syndromes, with beliefs that places (reduplicative paramnesia), people (Capgras, Fregoli), or events are transformed in identity or duplicated. These delusional syndromes can coexist.

RELATED NEUROLOGIC DISORDERS: CONFABULATION AND ANOSOGNOSIA

Confabulation and anosognosia are close kin to delusions. Confabulation refers to incorrect or distorted statements made without a conscious effort to deceive. Confabulation is usually associated with memory (medial temporal or diencephalic) and executive (bifrontal) dysfunction.^7-9 If retrieved information cannot be contextually and temporally labeled, past memories blur with current experience. Conscious guidance and maintenance of the search to link the results with past and current experience, or strategic recall, is often impaired.⁸ In contrast, the automatic and faster associative recall is intact. Deficits in self-monitoring and linking a memory with its source impairs reality monitoring and the ability to distinguish memory from internally generated thoughts.⁹

Although confabulation and content-specific delusions can coexist, they differ in features, time course, and neuroanatomy. Patients who confabulate can usually be redirected and corrected while those with delusions cannot. When confabulation and delusional misidentifications concur, confabulation usually resolves first.^10,11 The occurrence and resolution of ventromedial and orbital frontal lesions parallels the development and disappearance of confabulation.^7,12 Although confabulation and delusions are often caused by bilateral lesions, when pathology is unilateral, there is no lateralized predominance with confabulation,⁹ but right-sided lesions predominate with delusions.^6,13,14

Anosognosia is unawareness of a neurologic deficit, usually affecting vision (Anton syndrome) or movement (anosognosia for hemiplegia). The inability of self to recognize blindness or hemiplegia is striking. Anton syndrome is usually caused by bilateral occipital lesions, but can result from anterior visual system lesions, especially when combined with frontal pathology.¹⁵ Patients often confabulate about their visual loss; for example, “it's just bad lighting.” Babinski coined anosognosia to describe unawareness of left hemiplegia.¹⁶ Patients often insist their left arm and leg “can move fine” despite obvious weakness. Although anosognosia for hemiplegia after stroke often recovers over months, the initial false belief in the limb's strength is a delusion that resists rational explanations and visual demonstrations. Some patients deny ownership of their limb (asomatognosia), often claiming it belongs to someone else. Asomatognosia is a delusion in which the limb's relation to the self is lost, “Capgras syndrome affecting the arm.”¹⁸ Other patients personify the limb with names such as “Floppy Joe” or “Silly Jimmy,” hate the limb (misoplegia), or recognize the deficit but show no concern (anosodiaphoria).^17-19 Anosognosia for hemiplegia usually results from large nondominant hemisphere strokes involving parietal, frontal, and temporal lobes as well as the insula and subcortex.

REDUPLICATIVE PARAMNESIA

Pick reported a 67-year-old woman who developed amnesia, confabulations, paranoid delusions, and seizures after a stroke.²⁷ She believed that the Prague hospital and its doctors, attendants, and patients were simultaneously duplicated in her birth town. When the doctor asked how he could be there as well, she said was “very pleased to see him here too.” When asked about the “peculiarities” of the two clinics, she responded, “today's clinic is perhaps a continuation of the previous one.” Similarly, after a head injury, a man was repeatedly told and remembered that he was at the Jamaica Plain VA Hospital, but insisted the hospital was in his hometown of Taunton, Massachusetts.²⁹ Some patients misidentify but do not reduplicate their environment. Reduplicative paramnesia most often occurs in patients with neurodegenerative disorders, stroke, and head trauma. Among psychiatric patients, it is associated with bilateral anterior cortical atrophy.²⁸

Patients with reduplicative amnesia often confabulate, confusing memory and imagination. Like confabulation, reduplicative paramnesia is usually associated with executive and memory deficits, but visuospatial and geographic orientation skills are also often impaired.^7,25 Patients with reduplicative paramnesia recognize familiar places, landmarks, and objects, suggesting that the ventral occipitotemporal cortex that recognizes these stimuli is preserved. The lesions usually involve bifrontal or right frontal areas.^6,7,25 Frontal injury may disinhibit the intact familiarity and landmark areas in the temporal lobes while impairing self-monitoring, meta-memory, and error detection. Familiarity may be falsely triggered by novel stimuli but eludes error detection. Wish fulfillment and motivation may affectively color the choice of duplicated location. Virtually all patients believe that they are in or near their homes or hometowns.³³ After resolution of the delusion that the hospital was in their home, four patients “each claimed that their confabulated stories resulted from a desire to be at home.”³⁴

Rarely, patients believe that a familiar setting is reduplicated in a foreign place; i.e., foreign reduplicative paramnesia or Capgras for places. For example, a man with a right frontal hemorrhage returned home by taxi, recognized his wife and daughter, but was sure that his house was not his real home.²⁵ He remarked how “striking it was that the owners of this house had the same ornaments as he had in ‘his' house and what a coincidence it was that there were similar items beside the bed … ”

CAPGRAS SYNDROME

Capgras and Reboul-Lachaux reported a 53-year-old paranoid megalomanic woman “who transformed everyone in her entourage, even those closest to her, such as her husband and daughter, into various and numerous doubles.”²⁰ Delusional jealousy and grandeur began 8 years earlier, after four children died over a short period, leaving only a daughter. Later, she was convinced that her children were abducted and her surviving daughter was replaced by a look-alike. Thousands of doubles of her daughter passed before her eyes, “every day, sometimes many a day.” Her husband and even she were eventually replaced by doubles. Capgras attributed her delusions to an “agnosia of identification,” postulating that all sensory and memory images struggle between the emotional poles of familiarity and strangeness; he later proposed an Oedipal etiology.²¹

The Capgras delusion usually involves intimates—a spouse, sibling, child, or neighbor. The paradox of Capgras is the selective duplication of people with whom the patient has strong emotional bonds and associative memories. Capgras patients can consciously recognize familiar faces but cannot emotionally connect with them: the converse of prosopagnosia.³⁵ Prosopagnosia results from bilateral or right-sided lesions in the facial recognition areas (fusiform gyri). Patients may fail to recognize their spouse's or their own face but generate an unconscious autonomic skin resistance response to familiar faces. Nonconscious and conscious awareness are dissociated. Psychiatric and neurologic Capgras patients fail to generate autonomic responses when viewing photographs of familiar people or famous people.^35,36 In some patients, visual information reaches the facial recognition area leading to conscious recognition, but a temporal lesion may disconnect this from the limbic areas that infuse the sparkle of familiarity. This explanation cannot explain most Capgras cases since the temporal lobes may be spared and most cases involve visual and auditory modalities.⁶

The delusional misidentification-reduplication syndromes can be viewed as pathologic poles of decreased and increased familiarity. Capgras syndrome, the mirror sign, and foreign reduplicative paramnesia cause familiar people or places to become foreign. By contrast, in, Fregoli, intermetamorphosis, and reduplicative paramnesia syndromes, novel people and places “feel” very familiar. Paranoid ideation is common with Capgras syndrome, often preceding the delusion of the imposter.⁶ In contrast, paranoia is uncommon among patients with reduplicative paramnesia.^27-29

LESION LOCALIZATION IN DELUSIONAL MIS-IDENTIFICATION SYNDROMES

Neurologic patients with delusions usually have lesions in the right hemisphere and/or bifrontal areas.^{3,5–7,13,14,22–25,37–39} In some cases, a “two-hit” sequence may cause delusions: baseline generalized atrophy with a subsequent right hemisphere injury.^37,38 In one study, nine patients with right hemisphere infarctions at a stroke rehabilitation unit had frequent delusions. While size of the stroke did not correlate with delusions when compared to a control group, the presence of brain atrophy was a significant predictor of delusions.³⁸ When delusions occur in patients with widespread brain involvement, if pathology predominates in one hemisphere, it is usually the right. For example, delusional patients with Alzheimer disease have significantly more right frontal hypometabolism.^40,41

Reduplicative paramnesia and Capgras syndrome cases with unilateral brain lesions strongly implicate the right hemisphere, usually frontal with variable temporal or parietal involvement. ^{6,13,14,37,39} Among 69 patients with reduplicative paramnesia, lesions were primarily in the right hemisphere in 36 (52%), bilateral in 28 (41%), and left hemisphere in 5 (7%)³⁹—a sevenfold increase of right- over left-sided lesions (p < 0.0001). Similarly, among 26 Capgras patients, lesions were primarily in the right hemisphere in 8 (32%), bilateral in 16 (62%), and left-sided in 2 (7%)—a fourfold increase of right-over left-sided lesions (p < 0.06). For both delusional syndromes, many bilateral cases had maximal damage in the right hemisphere. Among 29 cases of delusional misidentification syndromes (overlap with prior review), all had right hemisphere pathology, while only 15 (52%) had left hemisphere damage.⁶ Fourteen had exclusively right hemisphere damage but none had isolated left-hemisphere damage. When lateralized lesions are found, right hemisphere lesions are more common in other delusional misidentification (Fregoli syndrome, mirror sign) and content specific delusions (Othello, erotomania).^24,30-32

Frontal lesions are strongly implicated in misidentification syndromes. Exclusively frontal lesions were associated with delusions in 10/29 (34.5%) cases⁶: four with right frontal and six with bifrontal lesions. None had lesions sparing the frontal lobes.⁶ Notably, temporal lesions were present in 7/11 (64%) patients who mistook familiar people, places, or body parts as foreign and 2/14 (14%) who mistook foreign objects or people as familiar. While frontal pathology is often critical for delusions to develop, associated temporal lesions may cause familiar places to appear foreign while temporal sparing may cause foreign places to appear familiar.

Observations in patients with bilateral neurodegenerative disorders supports that misidentification of familiar places as foreign is associated with temporal and frontal pathology. A patient with Alzheimer disease with foreign reduplicative paramnesia believed that his home was duplicated in another city; pathology was maximal in frontal and temporal association cortices.⁴² One study found neurodegenerative disorder in 38/47 (81%) Capgras patients, with Lewy body disease in 26 (55%).³ Many patients believed that there were multiple impostors, and held other delusions such as reduplicative paramnesia. Visual hallucinations, present in 30/38 (79%) of neurodegenerative patients, correlate with the severity of Lewy body deposition in the amygdala, and parahippocampal and inferior temporal cortices.⁴³ Dysfunction in these areas can cause paranoia and visual hallucinations. Patients with Lewy body disease may identify familiar faces, but cannot link the face and emotion. Frontal lobe dysfunction, a neuropsychological hallmark of Lewy body disease,⁴⁴ may prevent patients from recognizing their errors and changing their false beliefs. The frontotemporal lesions may lead patients to see familiar people or places as foreign; temporal lesions may cause paranoia.

PATHOGENESIS

A spectrum of cognitive and behavioral disorders may cause or contribute to delusions (table 2).^{2–6,13–15,45–47} Nearly ubiquitous frontal pathology supports the role of impaired executive, theory of mind, decision and prediction making, time estimation and sequencing, meta-memory, and working memory functions. Frontal dysfunction impairs the ability to monitor self and to recognize and correct inaccurate memories and familiarity assessments. The resistance of delusions to change despite clear evidence that they are wrong likely reflects frontal dysfunction. The right frontal lobe likely monitors the appropriateness of familiarity decisions, consistent with right frontal lesions in almost all delusional misidentification syndromes, while the right temporal lobe creates the glow of emotional familiarity.⁴⁸

The anterior parahippocampal cortex (perirhinal cortex, Brodmann areas 35 and 36) is activated by familiarity, while the hippocampus and posterior parahippocampal cortex mediate recollection.⁴⁹ Perirhinal cortex stimulation evokes déjà vu and déjà vécu (already experienced).⁵⁰ Further, the right hemisphere dominates in familiarity decisions^14,48; déjà vu is more common with right than left temporal lobe seizures or stimulation.^48,51 Lesions that destroy or isolate stimuli from right perirhinal cortex may lead to loss of familiarity (e.g., Capgras syndrome) while hyperfamiliarity (i.e., misidentifying strange people as familiar [Fregoli syndrome]) may result from overactivity in right perirhinal cortex from stimulation or disinhibition. Two cases of nondelusional hyperfamiliarity for faces resulted from left-sided lesions (lateral temporal-occipital and anterior cingulate),^52,53 possibly disinhibiting right hemisphere areas that imbue faces or places with familiarity.

Delusions may develop preferentially after right hemisphere lesions because of 1) loss of self-related functions such as monitoring of reality, memory, and familiarity,^6,14,48 and 2) left hemisphere overactivity after loss of right-sided influences. The right hemisphere dominates awareness and image of self and relating perceptual and emotional self to the external and internal environments.^6,14,48 Thus, right hemisphere lesions may cause delusions by disrupting the relation between and the monitoring of psychic, emotional, and physical self to people, places, and even body parts.^6,14 This explains why content-specific delusions involve people, places, or things of personal significance and distort their relation to the self. The right hemisphere dominates self-recognition,⁵⁴ emotional familiarity,^14,50 and ego boundaries.^6,14,55 An example is the “response-to-next-patient-stimulation,” found in patients with acute right hemisphere strokes.⁵⁵ When commands such as open your mouth were directed to the patient in the bed next to them, the stroke patients obeyed the commands. This inability to distinguish verbal information directed at others vs self is a disorder of the ego boundary.

Left hemisphere hyperactivity may play a critical role in the pathogenesis of delusions. Jackson recognized many dramatic positive symptoms result from intact brain areas released from control by damaged areas.⁵⁶ Lesions outside the right temporal lobe may cause nondelusional hyperfamiliarity syndromes by disinhibiting emotional familiarity. In corpus callosotomy patients, when an emotional visual stimulus is selectively presented to the right hemisphere, the left hemisphere may confabulate. One such patient blushed and giggled after her right hemisphere saw a nude picture. When asked what she saw, her left hemisphere responded, “Nothing, just a flash of light.” When asked why she was laughing—“Oh doctor, you have some machine!”⁵⁷ Another callosotomy patient saw a snow scene in the right hemisphere (left visual field) and chicken claw in the left hemisphere (right visual field). Asked to choose a picture card that related to what was seen, the left hand chose a shovel and the right hand picked a chicken. When asked what he saw: “I saw a claw and I picked the chicken, and you have to clean out the chicken shed with a shovel.”⁵⁸ Similarly, when a picture of a hurdler was flashed to the right hemisphere, the word “athlete” was offered, presumably by the right hemisphere. The left hemisphere then went on, “a basketball guy … had a uniform.”⁵⁹ These confabulatory responses reflect the left hemisphere's “creative and incorrect filling in.”⁵⁹ Gazzaniga referred to the left hemisphere's narrative talent that extends to fiction as the interpreter mechanism: “ … always hard at work, seeking the meaning of events. It is constantly looking for order and reason, even when there is none—which leads it continually to make mistakes. It tends to over-generalize, frequently constructing a potential past as opposed to a true one.”⁵⁹ Release of the left hemisphere's creative narrator from the monitoring of self, memory, and familiarity by the right frontal lobe may lead to excessive or false explanations. In callosotomy patients, testing is often done months after surgery and the frontal lobes are usually intact, accounting for the lack of delusions.

For visual perception and mental imagery, the right hemisphere is stronger at encoding overall patterns, representing specific instances, and mapping coordinate spatial relations. The left hemisphere encodes component parts, represents categories, and encodes categorical relations.⁶⁰ Spatially, the left hemisphere dominates at dual categorical choices such as up vs down and left vs right. In callosotomy patients, the right hemisphere can point to a state's location and then draw its shape, but the left hemisphere can tell whether state is north/south or east/west of another. Thus, a left hemisphere released from the right may be overbiased to categorize, but without the right hemisphere's gestalt and emotional familiarity. This combination may explain the bizarre invention of an impostor or duplicate. The left hemisphere recognizes “she is my wife,” but fails to receive other information (sparkle of familiarity, global gestalt, and relation to self) and concludes that “she is not my wife.” The conflict is resolved with a fabrication, a dual category: a duplicate or impostor. She looks like my wife, but she really isn't my wife.

Right frontal injury impairs monitoring of feedback from others and self, leading to false memories and delusions that resist erasure, despite evidence that they are incorrect. Similarly, in anosognosic patients, the left hemisphere of an adult with superior verbal intelligence cannot understand evidence (i.e., the right side is weak) that a young child immediately grasps linguistically or visually. The left hemisphere just does not get it. Delusions result from right hemisphere lesions. But it is the left hemisphere that is deluded.

Our knowledge of delusions is limited by our ability to comprehend the patient's irrational thought process. The hypothesis and mechanisms put forth in this article remain speculative. The presence of similar lesions without delusions argues against but is not a fatal flaw for the hypothesis. The pathogenesis of delusions likely includes many mechanisms that span overlapping psychological, cognitive, and neurologic disorders. Individual differences in the all three areas may interact to produce complex clinical patterns. Yet common elements may contribute to creation and persistence of delusions in diverse psychiatric and neurologic disorders. Future research should explore the psychological, cognitive, and physiologic-anatomic systems that change during the emergence and resolution of delusions, as well as strategies to treat delusions (e.g., reducing left hemisphere overactivity).