Left temporal lobe structural and functional abnormality underlying auditory hallucinations

“…and duration of hallucinations are typically scored from symptom scales like the Brief Psychiatric Rating Scale (BPRS; Ventura et al., 1993), the Positive and Negative Symptom Scale (PANSS; Kay et al., 1987) and Scales for Assessment of Negative and Positive Symptoms (SANS/SAPS; Andreasen, 1990).”

“neuropsycHological (DicHotic listening) stuDies In a neuropsychological study on auditory hallucinations, Green et al. (1994) used a simple dichotic listening procedure with pair-wise presentations of consonant–vowel (CV) syllables, and found that hallucinating patients failed to show a significant right ear advantage…”

“…pathways for speech sound perception are quite well mapped out, not the least from recent functional neuroimaging studies (Binder and Price, 2001; Hickok and Poeppel, 2007; Hugdahl et al., 1999), it can be assumed that auditory hallucinations have their neuronal, or ‘internal’, origin in the…”

“A glutamate hypothesis has been proposed for schizophrenia (see Carlsson et al., 1999; Kehrer et al., 2008; Olney and Farber, 1995), suggesting that glutamate function in addition to dopamine function may be altered in patients with schizophrenia.”

“…in e.g., the right ear has both ipsilateral and contralateral input to the temporal lobe processing areas, the contralateral pathways are more preponderant, and a dichotic presentation mode will further strengthen the input by blocking the ipsilateral input from the other ear (Kimura, 1967).”

“, 2000), and the Psychotic Symptoms Rating Scales (PSYRATS; Haddock et al., 1999).”

“structural neuroimaging stuDies Structural MRI studies have confirmed abnormality in the speech areas in the left temporal lobe in patients with schizophrenia, with reduced grey matter density and volume on the left side compared to the right side (e.g., Barta et al., 1990; Kubicki et al., 2002; Lawrie and Abukmeil 19…”

“…have confirmed abnormality in the speech areas in the left temporal lobe in patients with schizophrenia, with reduced grey matter density and volume on the left side compared to the right side (e.g., Barta et al., 1990; Kubicki et al., 2002; Lawrie and Abukmeil 1998; Neckelmann et al., 2006).”

“Frontiers in Neuroscience www.frontiersin.org May 2009 | Volume 3 | Issue 1 | 34 FOCUSED REVIEW published: 1 May 2009 doi: 10.3389/neuro.01.001.2009 Left temporal lobe structural and functional abnormality underlying auditory hallucinations in schizophrenia”

“Such experiences are also seen to occur among healthy population with a life-time prevalence of approximately 4–5% (Krabbendam and van Os, 2005; Tien, 1991).”

“…activation in temporal lobe areas (Dierks et al., 1999; Lennox et al., 2000; Shergill et al., 2004; Suzuki et al., 1993) and in other language-related areas, such as the thala- mus (Silbersweig et al., 1995), and Broca’s area (McGuire et al., 1993; see also Weiss and Heckers, 1999 for review).”

“structural neuroimaging stuDies Structural MRI studies have confirmed abnormality in the speech areas in the left temporal lobe in patients with schizophrenia, with reduced grey matter density and volume on the left side compared to the right side (e.g., Barta et al., 1990; Kubicki et al., 2002; Lawrie and Abukmeil 19…”

“However, while the classic symptom scales are limited to the frequency and duration of hallucinations, other scales are more focused on the themes and contents of the voices and whether the voices cause distress and/or disruption to everyday life, like the revised Beliefs About Voices Questionnaire (BAVQ-R; Chadwick e…”

“…CV- syllables dichotic listening paradigm typically results in a REA in healthy individuals, i.e., more correct reports for the right ear stimulus of the dichotic pair, indicating a left temporal lobe speech perception locus (see Hugdahl, 2003; Hugdahl and Andersson, 1986; Pollmann et al., 2002).”

“Hallucinations occur in 70–80% of patients with schizophrenia and often produce distress, functional disability, and behavioral dys-control (cf. Shergill et al., 1998).”

“A glutamate hypothesis has been proposed for schizophrenia (see Carlsson et al., 1999; Kehrer et al., 2008; Olney and Farber, 1995), suggesting that glutamate function in addition to dopamine function may be altered in patients with schizophrenia.”

“A glutamate hypothesis has been proposed for schizophrenia (see Carlsson et al., 1999; Kehrer et al., 2008; Olney and Farber, 1995), suggesting that glutamate function in addition to dopamine function may be altered in patients with schizophrenia.”

“…have confirmed abnormality in the speech areas in the left temporal lobe in patients with schizophrenia, with reduced grey matter density and volume on the left side compared to the right side (e.g., Barta et al., 1990; Kubicki et al., 2002; Lawrie and Abukmeil 1998; Neckelmann et al., 2006).”

“The results are supported by ERP-studies (e.g., Ford and Mathalon, 2005) showing that hallucinating patients have reduced or aberrant cortical activity to acoustic stimuli.”

“…or provided instructions to generate inner speech perceptions, when in the scanner, have resulted in decreased activation in the same brain areas in hallucinating patients compared to healthy controls (Zhang et al., 2008), also when compared with non-hallucinating patients (McGuire et al., 1996).”

“Such a view is also in agreement with other studies on auditory verbal hallucinations, for e.g., ‘mis-representations of inner experiences’ (Heinks-Maldonado et al., 2007), ‘mis- attribution of speech’ (Allen et al., 2007), ‘mis-attributed cognitions and inner speech’ (Kinderman, 2007) or that…”

“This has also been shown for cortical thickness, with thinning of the cortical mantle in the left superior temporal gyrus and in prefrontal areas, including the inferior and middle frontal gyrus (Nesvåg et al., 2008).”

“…CV- syllables dichotic listening paradigm typically results in a REA in healthy individuals, i.e., more correct reports for the right ear stimulus of the dichotic pair, indicating a left temporal lobe speech perception locus (see Hugdahl, 2003; Hugdahl and Andersson, 1986; Pollmann et al., 2002).”

“A common finding is that such morphological abnormalities correlate with frequency and duration of auditory hallucinations (e.g., Milev et al., 2003; Neckelmann et al., 2006; Shapleske et al., 2002; Shin et al., 2005).”

“…external stimuli have in general shown increased activation in temporal lobe areas (Dierks et al., 1999; Lennox et al., 2000; Shergill et al., 2004; Suzuki et al., 1993) and in other language-related areas, such as the thala- mus (Silbersweig et al., 1995), and Broca’s area (McGuire et al., 1993;…”

“…on auditory verbal hallucinations, for e.g., ‘mis-representations of inner experiences’ (Heinks-Maldonado et al., 2007), ‘mis- attribution of speech’ (Allen et al., 2007), ‘mis-attributed cognitions and inner speech’ (Kinderman, 2007) or that auditory hallucinations may be ‘competitions between…”

“In the Neckelmann et al. (2006) study, VBM was used for comparison of grey matter density in schizophrenia patients and healthy controls.”

“, Hugdahl, 2003) and brain imaging (Specht and Reul, 2003) studies have revealed a more complex and interactive pattern of speech localization in the brain, emphasizing ventral and dorsal areas (Hickok and Poeppel, 2007), most studies converge on the left temporal lobe as the core site for speech perception.”

“…MRI measures in the following sections. neuropsycHological (DicHotic listening) stuDies In a neuropsychological study on auditory hallucinations, Green et al. (1994) used a simple dichotic listening procedure with pair-wise presentations of consonant–vowel (CV) syllables, and found that…”

“…attention’ by Hugdahl and Andersson (1986), involves a bottom–up and top–down processing conflict in the sense that the bottom-up stimulus-driven effect pushes for a right ear response while the top–down instruction-driven effect pushes for a left ear response (cf. Thomsen et al., 2004).”

“…activation in temporal lobe areas (Dierks et al., 1999; Lennox et al., 2000; Shergill et al., 2004; Suzuki et al., 1993) and in other language-related areas, such as the thala- mus (Silbersweig et al., 1995), and Broca’s area (McGuire et al., 1993; see also Weiss and Heckers, 1999 for review).”

“Frontiers in Neuroscience www.frontiersin.org May 2009 | Volume 3 | Issue 1 | 37 speech perception (see also Hugdahl et al., 2008).”

“Such a hypothesis is supported by the findings of Rund et al. (2006), that patients with schizophrenia are impaired in executive and cognitive control functions that have a prefrontal localization.”

“…in the absence of external stimuli have in general shown increased activation in temporal lobe areas (Dierks et al., 1999; Lennox et al., 2000; Shergill et al., 2004; Suzuki et al., 1993) and in other language-related areas, such as the thala- mus (Silbersweig et al., 1995), and Broca’s area…”

“…et al., 2007), ‘mis- attribution of speech’ (Allen et al., 2007), ‘mis-attributed cognitions and inner speech’ (Kinderman, 2007) or that auditory hallucinations may be ‘competitions between auditory stimuli and competition for physiological resources in the temporal cortex’ (Hubl et al., 2007).”

“…and the neural pathways for speech sound perception are quite well mapped out, not the least from recent functional neuroimaging studies (Binder and Price, 2001; Hickok and Poeppel, 2007; Hugdahl et al., 1999), it can be assumed that auditory hallucinations have their neuronal, or…”

“See also Woodruff (2004) for further discussion of the neuropsychology of auditory hallucinations.”

“A common finding is that such morphological abnormalities correlate with frequency and duration of auditory hallucinations (e.g., Milev et al., 2003; Neckelmann et al., 2006; Shapleske et al., 2002; Shin et al., 2005).”

“(1994) have later been reproduced in several laboratories (e.g., Conn and Posey, 2000; Hugdahl et al., 2008; Løberg et al., 2004; Rossell and Boundy, 2005).”

“In her meta-analysis of structural abnormality in schizophrenia, Williams (2008) did not find evidence for a right temporal lobe abnormality, thus supporting a view that the grey matter abnormality is uniquely related to the left hemisphere.”

“In addition to the standard procedure, the paradigm can also be used to study attentional and executive control functions, similar as seen in the Stroop-task (Lund-Johansen et al., 1996).”

“The findings of Green et al. (1994) have later been reproduced in several laboratories (e.g., Conn and Posey, 2000; Hugdahl et al., 2008; Løberg et al., 2004; Rossell and Boundy, 2005). training in tHe DicHotic listening situation to suppress tHe voices An interesting extension of the dichotic…”

“A common finding is that such morphological abnormalities correlate with frequency and duration of auditory hallucinations (e.g., Milev et al., 2003; Neckelmann et al., 2006; Shapleske et al., 2002; Shin et al., 2005).”

“…or provided instructions to generate inner speech perceptions, when in the scanner, have resulted in decreased activation in the same brain areas in hallucinating patients compared to healthy controls (Zhang et al., 2008), also when compared with non-hallucinating patients (McGuire et al., 1996).”

“A relationship between hallucinations and other positive symptoms was found by Løberg et al. (2006), using structural equation modeling to statistically model the association from performance on the dichotic listening task.”

“The findings of Green et al. (1994) have later been reproduced in several laboratories (e.”

“In a mini-review, Sommer et al. (2003) also concluded that ‘our results showed that language related areas in the left hemisphere were significantly more activated than the right-sided homotope regions’ (p. 217).”

“However, the results have varied, Fiszdon et al. (2005) failed to show any training effects on auditory hallucinations, while Hatashita-Wong and Silverstein (2003) found indications of improvement.”

“The findings of Green et al. (1994) have later been reproduced in several laboratories (e.g., Conn and Posey, 2000; Hugdahl et al., 2008; Løberg et al., 2004; Rossell and Boundy, 2005). training in tHe DicHotic listening situation to suppress tHe voices An interesting extension of the dichotic…”

“Functional abnormalities in these networks may be associated with structural brain changes (Hugdahl et al., 2009; Bassett and Bullmore, 2009; Horn et al., 2009).”

“…cortex, such that external stimuli are not capable of producing further activation sufficient to overcome the ongoing, spontaneous neural activity (Hugdahl et al., 2009), or an aberrant attentional bias, such that the prefrontal top-down control mechanisms do not bias the auditory cortex…”

“, 2000) and in functional magnetic resonance imaging (Hugdahl et al., 2009).”

“, brain circuits necessary for adequate self-monitoring, inhibitory control and goal-directed behaviour) has been proposed to underlie AVH in addition to deficient speech-processing networks.(4,6) However, since we investigated participants under resting-state conditions, the precise cognitive or affective functions o…”

“However, all existing models of AVH assume that dysfunctional activation intrudes into ongoing neural and cognitive processing (Hugdahl et al., 2009; see Jones, 2008, for a critique of current models).”

“A growing body of neuroimaging research has provided support for a neurobiological basis of AVH (Hugdahl et al. 2009; Jardri et al. 2011; Palaniyappan et al. 2012; Modinos et al. 2013) and also for the ef fi cacy of various treatment strategies.”

“The right ear signal will thus have direct access to the speech processing centres in the speech dominant left hemisphere, which as a consequence will result in more correct reports for the right ear stimulus (see Hugdahl et al., 2009 for further details).”

“Thus, functional dysfunctions in brain networks may result from structural changes both in WM and in GM [32, 33].”

“The planum polare is involved in controlling prosodic and attention-related auditory processes (Jancke, Buchanan, Lutz, & Shah, 2001 ; Meyer, Friederici, & von Cramon, 2000 ), and the STS is a brain area known to integrate information from different modalities (Oechslin et al, 2010 ; Hugdahl, Loberg, & Nygard, 2009 ;…”

“AVHs could be seen as a “marker” of a psychotic episode (Wing et al., 1974; Shergill et al., 1998; Hugdahl et al., 2009), occurring in more than 70% of patients with a schizophrenia diagnosis.”

“…domain (e.g., perception and attention), which are critically involved in AH and show individual variation from normal to pathological behavior (see Hugdahl et al., 2009a,b) as well as domains which have been relatively understudied in relation to AH (e.g., Systems for Social Processes; see Ford…”

“The specificity of the PT in schizophrenia suggests that it is amajor contributor to the structural abnormalities associated that have previously shown to be associatedwith functional abnormalities in the left temporal lobe (Hugdahl et al., 2009; Ethridge et al., 2012).”

“(57) found overlapping activation in a large-scale network to occur with a range of different cognitive tasks implicating the prefrontal cortex [see also Ref.”

“While positive symptoms are related to the temporal lobe and limbic areas (48, 49), contrastingly, negative symptoms in schizophrenia appear to be related to deficits in specific regions generating hypofrontality (50).”

“We have previously used a modified dichotic listening (DL) task with simple speech sounds and with instructions to focus attention on either the left or right ear stimulus (Hugdahl and Andersson, 1986; Løberg et al., 1999; Hugdahl et al., 2009a).”

“…et al., 2013) as well as reduced REA (Løberg et al., 1999), on the other hand an increased activation of the STG has also been shown in schizophrenic patients during the experience of auditory hallucinations (Hugdahl et al., 2009; Hugdahl et al., 2003; Lennox et al., 2000; Løberg et al., 2004).”

“Immediate cessation of hallucination with cathodal stimulation (inhibitory effect) at left temporoparietal region supports the postulated hyperactivity of this brain region to underlie the pathogenesis of auditory hallucinations [7].”

“Intriguingly, extraneous auditory stimuli have been associated with attenuated neuronal activity in the superior temporal cortices of the brain in patients with AVHs (Hugdahl et al., 2009).”

“Auditory hallucinations can be linked to abnormally elevated resting state activity in the auditory cortex itself, irregular modulation of the auditory cortex by anterior cortical midline structures as part of the DMN, and neural miscommunication between auditory cortical resting state shifts and stimulus triggered ac…”

“The effort mode network, on the other hand, is assumed to involve areas in the inferior and middle frontal gyrus, supplementary motor area (SMA), anterior cingulate, posterior temporal cortex, and parietal cortex (cf. Fox and Raichle, 2007; Hugdahl et al., 2009; Nygård et al., 2012).”

“Disinhibition of language processing centres may result in an inability to distinguish between inner and external speech, resulting in a misattribution of inner speech as externally generated 41–43 .”

“It was also suggested that a cognitive control deficit results in a failure of top-down inhibition of bottom-up erroneous percept (Hugdahl et al., 2009).”

“…2010 doi: 10.1111/j.1528-1167.2009.02338.x FULL-LENGTH ORIGINAL RESEARCH 610 speech sounds, similar to what has been found in patients with schizophrenia (Hugdahl et al., 2009), that would support a unique neuronal representation for auditory hallucinations cutting across diagnostic groups.”

“…al., 2003; Hugdahl et al., 2009; Lennox et al., 2000; Løberg et al., 2004), which has been proposed to be the cerebral substrate of hearing voices (Hugdahl, 2009), would be modulated by the right-hemispheric activity due to the negative valence of voices’ content, leading to an absence of…”

“the DMN and simultaneously upregulate the EMN in cognitive situations requiring effory (12).”

“The forced-left total performance group difference further validated the focus on attentional control to explain the findings, as this condition was suggested to be especially sensitive to attention control deficits (Hugdahl et al., 2009).”

“A possible empirical test to investigate a potential association between AVHs and abnormal lateralization of speech perception is the dichotic listening task (DLT) (Green et al., 1994; Hugdahl et al., 2009; Løberg et al., 2004).”

“Therefore, when neurons of the temporal lobe are damaged, a variety of mental disorders are likely to occur, such as cognitive decline, memory reduction, or subjective emotional instability (Hugdahl et al., 2009).”

“In patients with schizophrenia, previous studies suggested that structural changes in frontal and temporal lobes might be related with their impairments in executive function, hallucination and negative symptoms (36, 41, 42).”

“information about his or her symptoms (Karlsson, 2005). To that end, a patient might feel more comfortable being honest and forthcoming about his or her symptoms with a therapist who speaks his or her native language (Ibaraki & Hall, 2014), which could help explain the pattern of results obtained for positive symptoms…”

“Together the STG, mPFC, PCC, and ACC are considered part of a functional brain circuit - a “ self-reference network ” - associated with the onset and maintenance of AHs in SZ (Hugdahl, 2015; Hugdahl et al., 2009; Northoff and Qin, 2011).”

“These functions may be disrupted by auditory hallucinations resulting in the classic psychotic symptoms of SCZ (8), which differ from those seen in BPD (9).”

“This theory is supported by neuroimaging findings that suggest patients with AVHs also show deficits in processing exogenously presented sounds (David et al., 1996; Woodruff et al., 1997; Hugdahl et al., 2009; Kompus et al., 2011).”

“The latter finding is consistent with earlier research indicating a relationship between frequency of auditory hallucination and levels of perceived control over voices (Honig et al., 1998; Hugdahl et al., 2009; Leudar et al., 1997).”

“6 More recently, evidence is mounting for a role of the paracingulate sulcus (PCS), which has been reported to be involved in reality monitoring processing.”

“However, none of the previous studies have demonstrated a direct link between hemispheric differences for FA-values, and for difference in asymmetry between AVH+ and AVH- patients, indicating a structural correlate to known behavioral and functional differences between AVH+ and AVH- patients (cf. Falkenberg, Westerhau…”

“Finally, two major features of schizophrenia pathology, hallucinations and delusions, involve, in addition to abnormalities in cognitive control [20, 21] and in perceptual and attentional processes [22], also abnormalities in the sense of agency [23].”

“, 2016, 2017), other authors (Hugdahl et al., 2009; Guerrero-Pedraza et al., 2012) have suggested that both hypo- and hyper-activation might be necessary for efficient cognitive functioning because the upregulation of one network will require the down-regulation of another (Nygard et al.”

“considerable amount of evidence indicating left hemisphere dysfunction in schizophrenia and schizoaffective disorder (12-15).”

“The SCID-I reliability for this team is good (K = 0.76) (Joa et al., 2007) and the weekly staff discussions minimised the risk of drift.”

“Previous brain imaging studies have provided a wealth of information on the abnormal structural and functional connectivity of schizophrenia patients with AHs [40–44].”

“While hallucinations on LSD tend to be more visual than auditory, both psychedelic-induced and schizophrenic hallucinations share the common characteristic of misattributing internally generated perception to the external world (Hugdahl et al., 2009).”

“[1,3-5] Although many potential mechanisms may underpin the effects of tDCS on AVHs, current evidence suggests the primary effect results from neuromodulation of cortical excitability at the left temporoparietal junction (TPJ) and left dorsolateral prefrontal cortex (DLPFC).[1,6,7] However, assessing the effects of tD…”

“Therefore, when neurons of the temporal lobe are damaged, a variety of mental disorders are likely to occur, such as cognitive decline, memory reduction, or subjective emotional instability [30].”

“Healthy individuals can use attentional focus to distinguish between different sounds presented simultaneously in auditory tests, but patients with frequent auditory hallucinations lack this “top-down” control (Hugdahl et al., 2009).”