Supriya Syal - Academia.edu (original) (raw)

Papers by Supriya Syal

BACKGROUND: Social anxiety disorder (SAD) is characterized by excessive anxiety about social inte... more BACKGROUND: Social anxiety disorder (SAD) is characterized by excessive anxiety about social interaction or performance situations, leading to avoidance and clinically significant distress. A growing literature on the neurobiology of SAD has suggested that the reward/avoidance basal ganglia circuitry in general and the glutamatergic system in particular may play a role. In the current study, we investigated 1H-Magnetic resonance spectroscopy (1H-MRS) concentrations in cortical, striatal, and thalamic circuitry, as well as their associations with measures of social anxiety and related symptoms, in patients with primary SAD.
METHODOLOGY:
Eighteen adult individuals with SAD and 19 age- and sex- matched controls participated in this study. 1H-MRS was used to determine relative metabolite concentrations in the anterior cingulate cortex (ACC) using single voxel spectroscopy (reporting relative N-acetyl-aspartate (NAA), N-acetyl-aspartate with N-acetyl-aspartyl-glutamate (NAA+NAAG), glycerophosphocholine with phosphocholine (GPC+PCh), myo-inositol, glutamate (Glu), and glutamate with its precursor glutamine (Glu+Gln)), and the caudate, putamen and thalami bilaterally using two dimensional chemical shift imaging (reporting relative NAA+NAAG and GPC+PCh). Relationships between metabolite concentrations and measures of social anxiety and related symptoms were also determined. Measures of social anxiety included symptom severity, blushing propensity, and gaze anxiety/avoidance.
RESULTS:
We found, first, decreased relative glutamate concentration in the ACC of SAD and changes in myo-inositol with measures of social anxiety. Second, NAA metabolite concentration was increased in thalamus of SAD, and choline metabolite concentrations were related to measures of social anxiety. Lastly, choline metabolite concentration in the caudate and putamen showed changes in relation to measures of social anxiety.
CONCLUSION:
These findings are consistent with evidence that the reward/avoidance basal ganglia circuitry, as well as the glutamatergic system, play a role in mediating SAD symptoms.

In rodents, there is abundant evidence for the involvement of the opioid system in the processing... more In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are disregarded by subjects scoring high on depressive mood who are low in reward drive. We investigated whether a single 2 mg administration of the mixed mu-opioid agonist/kappa-antagonist, buprenorphine, would influence short-term memory for happy, angry or fearful expressions relative to neutral faces. Healthy human subjects (n = 38) participated in a randomized placebo-controlled within-subject design, and performed an emotional face relocation task after administration of buprenorphine and placebo. We show that, compared to placebo, buprenorphine administration results in a significant improvement of memory for happy faces. Our data demonstrate that acute manipulation of the opioid system by buprenorphine increases short-term memory for social reward cues.

Sociality and cooperation are benefits to human cultures but may carry unexpected costs. We sugge... more Sociality and cooperation are benefits to human cultures but may carry unexpected costs. We suggest that both the human experience of pain and the expression of distress may result from many causes not experienced as painful in our close primate relatives, because human ancestors motivated to ask for help survived in greater numbers than either the thick-skinned or the stoic.

Metabolic Brain Disease, 2014

Although animal evidence indicates that early life trauma results in pervasive hippocampal defici... more Although animal evidence indicates that early life trauma results in pervasive hippocampal deficits underlying spatial and cognitive impairment, visuo-spatial data from adult humans with early childhood adversity are lacking. We administered 4 tests of visuo-spatial ability from the Cambridge Neuorpsychological Test Automated Battery (CANTAB) to adults with a history of childhood trauma (measured by the Childhood Trauma Questionnaire) and a matched sample of healthy controls (trauma/control = 27/28). We observed a significant effect of trauma history on spatial/ pattern learning. These effects could not be accounted for by adverse adult experiences, and were sex-specific, with prior adversity improving performance in men but worsening per- formance in women, relative to controls. Limitations include the small sample size and reliance of our study design on a retrospective, self report measure. Our results suggest that early adversity can lead to specific and pervasive deficits in adult cognitive function.

Neuropsychopharmacology

The South African endemic plant Sceletium tortuosum has a long history of traditional use as a ma... more The South African endemic plant Sceletium tortuosum has a long history of traditional use as a masticatory and medicine by San and Khoikhoi people and subsequently by European colonial farmers as a psychotropic in tincture form. Over the past decade, the plant has attracted increasing attention for its possible applications in promoting a sense of wellbeing and relieving stress in healthy individuals and for treating clinical anxiety and depression. The pharmacological actions of a standardized extract of the plant (Zembrin) have been reported to be dual PDE4 inhibition and 5-HT reuptake inhibition, a combination that has been argued to offer potential therapeutic advantages. Here we tested the acute effects of Zembrin administration in a pharmaco-fMRI study focused on anxiety-related activity in the amygdala and its connected neurocircuitry. In a double-blind, placebo-controlled, cross-over design, 16 healthy participants were scanned during performance in a perceptual-load and an emotion-matching task. Amygdala reactivity to fearful faces under low perceptual load conditions was attenuated after a single 25mg dose of Zembrin. Follow-up connectivity analysis on the emotion- matching task showed that amygdala–hypothalamus coupling was also reduced. These results demonstrate, for the first time, the attenuating effects of S. tortuosum on the threat circuitry of the human brain and provide supporting evidence that the dual attenuating effects of S. tortuosum on the threat circuitry of the human brain and provide supporting evidence that the dual 5-HT reuptake inhibition and PDE4 inhibition of this extract might have anxiolytic potential by attenuating subcortical threat responsivity

J. T Weeks (Eds.), The Wiley-Blackwell Handbook on Social Anxiety Disorder, Wiley Blackwell, 2014

Considered through the lens of social neuroscience, social anxiety disorder (SAD) can be conceptu... more Considered through the lens of social neuroscience, social anxiety disorder (SAD) can be conceptualized as an aberration of social behavior, and by proxy, the social brain. Because of the fundamentally social structure of the human ecological niche, a disorder of the social brain is likely to impinge upon numerous areas of human behavior. In the first part of this chapter, we review key functional neuroimaging and behavioral research findings on social brain function in SAD. The second section of this chapter reviews recent social anxiety research that has explored additional dimensions of social function, as well as recommends research directions that remain unvisited in SAD thus far. We emphasize the importance of multi-dimensional and integrative approaches to gaining a holistic understanding of this complex and intriguing disorder.

Behavioral and Brain Sciences, 2013

Language is a social act. We have previously argued that language remains embedded in sociality b... more Language is a social act. We have previously argued that language remains embedded in sociality because the motivation to communicate exists only within a social context. Schilbach et al.underscore the importance of studying linguistic behavior from within the motivated, socially interactive frame in which it is learnt and used, as well as provide testable hypotheses for a participatory, second-person neuroscience approach to language learning.

Metabolic Brain Disease, 2012

While a number of studies have explored the functional neuroanatomy of social anxiety disorder (... more While a number of studies have explored the
functional neuroanatomy of social anxiety disorder (SAD),
data on grey matter integrity are lacking. We conducted
structural MRI scans to examine the cortical thickness of
grey matter in individuals with SAD. 13 unmedicated adult
patients with a primary diagnosis of generalized social anxiety
disorder and 13 demographically (age, gender and
education) matched healthy controls underwent 3T structural
magnetic resonance imaging. Cortical thickness and subcortical
volumes were estimated using an automated
algorithm (Freesurfer Version 4.5). Compared to controls,
social anxiety disorder patients showed significant bilateral
cortical thinning in the fusiform and post central regions.
Additionally, right hemisphere specific thinning was found
in the frontal, temporal, parietal and insular cortices of
individuals with social anxiety disorder. Although uncorrected
cortical grey matter volumes were significantly lower
in individuals with SAD, we did not detect volumetric
differences in corrected amygdala, hippocampal or cortical
grey matter volumes across study groups. Structural differences
in grey matter thickness between SAD patients and
controls highlight the diffuse neuroanatomical networks involved in both social anxiety and social behavior. Additional
work is needed to investigate the causal mechanisms
involved in such structural abnormalities in SAD.

Metabolic Brain Disease

We conducted a systematic review and metaanalysis of proton magnetic resonance spectroscopy (1HM... more We conducted a systematic review and metaanalysis
of proton magnetic resonance spectroscopy (1HMRS)
studies comparing autism spectrum disorder (ASD)
patients with healthy controls, with the aim of profiling
ASD-associated changes in the metabolites N-acetylaspartate
(NAA) and Creatine (Cr). Meta-regression models
of NAA and Cr levels were employed, using data from 20
eligible studies (N0852), to investigate age-dependent differences
in both global brain and region-specific metabolite levels,
while controlling for measurementmethod (Cr-ratio versus
absolute concentrations). Decreased NAA concentrations that
were specific to children were found for whole-brain grey and
white matter. In addition, a significant decrease in NAA was
evident across age categories in the parietal cortex, the cerebellum,
and the anterior cingulate cortex. Higher levels of Cr
were observed for ASD adults than children in global grey
matter, with specific increases for adults in the temporal lobe
and decreased Cr in the occipital lobe in children. No differences
were found for either NAA or Cr in the frontal lobes.
These data provide some evidence that ASD is characterized
by age-dependent fluctuations in metabolite levels across the
whole brain and at the level of specific regions thought to
underlie ASD-associated behavioural and affective deficits.
Differences in Cr as a function of age and brain region suggests caution in the interpretation of Cr-based ratio measures of metabolites. Despite efforts to control for sources of heterogeneity considerable variability in metabolite levels was observed in
frontal and temporal regions, warranting further investigation.

Psychoneuroendocrinology, 2012

In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the re... more In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the reduction of fear in particular. In humans, while there is evidence that the opioid antagonist naloxone acutely enhances the acquisition of conditioned fear, there are no corresponding data on the effect of opioid agonists in moderating responses to fear. We investigated whether a single 0.2 mg administration of the mu-opioid agonist buprenorphine would decrease fear sensitivity with an emotion-recognition paradigm. Healthy human subjects participated in a randomized placebo-controlled within-subject design, in which they performed a dynamic emotion recognition task 120 min after administration of buprenorphine and placebo. In the recognition task, basic emotional expressions were morphed between their full expression and neutral in 2% steps, and presented as dynamic video-clips with final frames of different emotional intensity for each trial, which allows for a fine-grained measurement of emotion sensitivity. Additionally, visual analog scales were used to investigate acute effects of buprenorphine on mood. Compared to placebo, buprenorphine resulted in a significant reduction in the sensitivity for recognizing fearful facial expressions exclusively. Our data demonstrate, for the first time in humans, that acute up-regulation of the opioid system reduces fear recognition sensitivity. Moreover, the absence of an effect of buprenorphine on mood provides evidence of a direct influence of opioids upon the core fear system in the human brain.

Developmental Science, 2011

Alteration of the organization of social and motivational neuroanatomical circuitry must have bee... more Alteration of the organization of social and motivational neuroanatomical circuitry must have been an essential step in the
evolution of human language. Development of vocal communication across species, particularly birdsong, and new research on the neural organization and evolution of social and motivational circuitry, together suggest that human language is the result of
an obligatory link of a powerful cortico-striatal learning system, and subcortical socio-motivational circuitry.
Introduction
The essential modification in human evolution enabling
language has been addressed for decades. In adults,
language is demonstrably dependent on the cortex, so the
essential evolutionary modification for language has
reasonably been sought in the quality or quantity of
cortical computations found there. The crystallized
product of a lifelong learning process may not be the best
source of insight, however, about what initial alterations
permitted it. Language plasticity after early damage
raises the most perplexing questions about what in the
cortex allows language. The right half of the cortex may
be removed, or the left half, and language still develops.
The frontal cortex may be removed or severely reduced.
Uncomfortably for capacity arguments, total cortical
volume may be reduced wholesale by prenatal genetic
accident, such as Down’s syndrome, or by postnatal
accident, and yet language will often survive (Bates,
Reilly, Wulfeck, Dronkers, Opie, Fenson, Kiz, Jeffries,
Miller & Herbst, 2001; Bates, 2004). An individual may
be deaf, blind, or blind and deaf together, and with
dedicated tutelage will still learn language with what
remains. What conceivable sensory specialization or
cortical alteration could survive these assaults?
We will remain agnostic on the cognitive and cortical
architecture of language. Instead, we will highlight the
changes in human sociality and its motivational correlates,
and explore motivation’s mechanistic links to
language. Of course, unique aspects of human social
structure have already been explored widely and at
multiple levels. A general coupling between growth of the
neocortex and increasing social complexity in primates
has been observed (Dunbar & Schultz, 2007). Demonstrations
of how human cultures have solved the problem
of stabilization of non-kin altruism, that is, how to stabilize
social structures and eliminate cheating such that
the manifest benefits of extended altruism to social
groups can be had, have been explored in number
(Wilson, Van Vugt & O’Gorman, 2008; Bowles, 2006;
Richerson & Boyd, 2005; Warneken & Tomasello, 2008;
Pagel, 2009). In development, human children, contrasted
with young chimpanzees, attend to social cues,
share information, join games and generally cooperate,
serving a form of social learning seen only in humans
(Moll & Tomasello, 2007; see also Preston & de Waal,
2001). What is new, and what we are now able to do is
place human social behavior more accurately in a comparative
and neuroanatomical context, as a transformation
of our understanding of the neural circuitry of
sociality and its evolutionary variation has occurred
(Newman, 1999; Goodson, 2005) (see Figure 1).
Making explicit this paper’s goals: why evolution and
development of social communication in non-human
animals should directly inform language development
and evolution in humans
We will explore the recent advances in the understanding
of the social behavior network and its evolutionary
variations, highlighting some key findings for those
interested in language learning and comparative cognition.
We will make some specific proposals about what
kind of neuroanatomical circuitry might be changed
to link communication with the most fundamental
pleasure and reward in human infants. Further, we will
hypothesize that such a link constitutes a socio-motivational
‘gate’ necessary and sufficient for the evolution

Infancy, 2010

Two studies illustrate the functional significance of a new category of prelinguistic vocalizing—... more Two studies illustrate the functional significance of a new category of prelinguistic vocalizing—object-directed vocalizations (ODVs)—and show that these sounds are connected to learning about words and objects. Experiment 1 tested 12-month-old infants’ perceptual learning of objects that elicited ODVs. Fourteen infants’ vocalizations were recorded as they explored novel objects. Infants learned visual features of objects that elicited the most ODVs but not of objects that elicited the fewest vocalizations. Experiment 2 assessed the role of ODVs in learning word–object associations. Forty infants aged 11.5 months played with a novel object and received a label either contingently on an ODV or on a look alone. Only infants who received labels in response to an ODV learned the association. Taken together, the findings suggest that infants’ ODVs signal a state of attention that facilitates learning.